CONCISE REVIEW FOR CLINICIANS

Wernicke EncephalopathydClinical Pearls

Shirshendu Sinha, MBBS; Archish Kataria, MBBS; Bhanu Prakash Kolla, MD;
Nuria Thusius, MD; and Larissa L. Loukianova, MD, PhD

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Learning Objectives: On completion of this article, you should be able
to (1) recognize the historical background, epidemiology, and pathogen-
esis of Wernicke encephalopathy (WE), (2) recognize the signs and symptoms
of WE, and (3) demonstrate knowledge of practice parameters for the use of
thiamine in WE.
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Abstract

Wernicke encephalopathy (WE) was first described by Carl Wernicke in 1881. WE is caused by thiamine
deficiency. Alcoholism is the most common etiologic factor associated with WE in the United States, but
it can occur in any patient with a nutritional deficiency state such as hyperemesis gravidarum, intestinal
obstruction, and malignancy. WE is a clinical diagnosis. The common findings include mental status
changes, ocular dysfunction, and a gait apraxia, present in only 10% of cases. Only a few cases of WE are
diagnosed before death. Approximately 80% of patients with untreated WE have development of Kor-
sakoff syndrome, which is characterized by memory impairment associated with confabulation. The
initial clinical diagnosis of WE is critical, keeping in mind that the classic triad of symptoms is often
absent. Recognition of nutritional deficiency and any portion of the classic triad should prompt treat-
ment. Additionally, hypothermia, hypotension, and coma should raise clinical suspicion for the disease.
Primary treatment includes timely administration of thiamine, for which the route and dosage remain
controversial. Clinical judgment should be exercised in diagnosis and treatment (dosage, frequency,
route of administration and duration) in all cases of WE. Overdiagnosis and overtreatment may be
preferred to prevent prolonged or persistent neurocognitive impairments given the excellent safety

Mayo Clin Proc. n June 2019;94(6):1065-1072 n https://doi.org/10.1016/j.mayocp.2019.02.018 1065

www.mayoclinicproceedings.org n ª 2019 Mayo Foundation for Medical Education and Research

profile of thiamine. Further prospective research is warranted to better understand the disease
biology, risk factors, and treatment recommendations.
ª 2019 Mayo Foundation for Medical Education and Research
W
ernicke encephalopathy (WE)
is an often underrecognized
condition with estimates sug-
gesting that only about 15% of cases of WE
are diagnosed before death.1 The primary
etiology of WE is thiamine deficiency.
Although alcoholism is the most common
predisposing factor in the United States,
WE can also occur in patients with nutri-
tional deficiency states such as hyperemesis
gravidarum, intestinal obstruction, bariatric
surgery, cancer chemotherapy, hemodialysis,
and malignant diseases.2 One of the index
cases that Carl Wernicke described in 1881
was a 20-year-old nonalcoholic seamstress
who attempted suicide by ingesting sulfuric
acid and subsequently had development of
pyloric stenosis leading to a nutritional defi-
ciency of thiamine.2 WE can occur in pediat-
ric patients, with most of the cases secondary
to malignancy.3 In some individuals, thia-
mine deficiency may not be apparent. In
such subclinical cases, WE can be unmasked
by administration of a carbohydrate load
(iatrogenic) and diagnosis of conditions
such as hypomagnesemia, thyrotoxicosis,
and refeeding syndrome among others.
THIAMINE DEFICIENCY AND RESULTANT
BRAIN DAMAGE
WE is the most important encephalopathy
occurring because of a single vitamin defi-
ciency. Thiamine is an important cofactor
for several key enzymes responsible for the
maintenance of cerebral energy homeostasis.
These include a-ketoglutarate dehydroge-
nase and pyruvate dehydrogenase of the
Krebs cycle and transketolase of the pentose
phosphate pathway4 (Figure). Toxic inter-
mediates accumulate due to a decrease in
enzyme activity. Thiamine deficiency also
impairs the conversion of pyruvate to acetyl
coenzyme A. This, in turn, increases lactic
acid production. All of these intermediates
induce tissue injury by inhibiting meta-
bolism in areas of the brain with high meta-
bolic requirement and thiamine turnover.
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1066 Mayo Clin Proc.
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n Mayo Clin Proc. 2019;94(6):1065-1072
Patients with alcoholism and malnutrition
are also often deficient in magnesium, a
cofactor for normal functioning of
thiamine-dependent enzymes and neuro-
chemical transmission.5 The brain lesions
of WE follow a symmetric distribution
among structures that surround the third
and fourth ventricles and the aqueduct.
The most commonly affected structures are
mammillary bodies, involved in up to 80%
of cases of WE.6 Lesions in the dorsomedial
thalamus have been associated with reported
memory loss in WE. Atypical lesions, usually
associated with nonealcohol-related cases of
WE, can be located in the cerebellum, ver-
mis, cranial nerve nuclei, red nuclei, dentate
nuclei, caudate nuclei, splenium, and cere-
bral cortex.2
Clinical Features
The classic clinical triad of the syndrome
consists of mental status changes, ophthal-
moplegia, and gait ataxia (Table 1). Clini-
cians are taught to expect a very distinct,
unique, and striking presentation, which
may in fact be present in only 10% of cases.7
Absence of such a stereotypical presentation
reinforces the misconception that WE is
rare. Clinicians, particularly those working
in the emergency setting, need to be aware
of the clinical variability of WE because
most patients will present to the emergency
department and the disorder will remain un-
diagnosed.2 Consequently, the syndrome is
most often recognized only at autopsy. The
most consistent characteristic of the syn-
drome is a change in mental status.7 The
cognitive changes range from apathy and
mild neurocognitive symptoms to severe
symptoms including, in rare situations,
coma.8 The second most common character-
istic is ophthalmoplegia, but other ocular
findings may be present. Complete ophthal-
moplegia occurs rarely, whereas horizontal
nystagmus is the most common ocular ab-
normality.8 The other ocular findings
include sixth nerve palsy, ptosis, retinal
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THIAMINE DEFICIENCY AND WERNICKE ENCEPHALOPATHY

Pentose phosphate pathway

Glucose
Oxidative Ribulose-5- Nonoxidative
phase phase Ribulose-5-
phosphate
Glucose-6-phosphate phosphate
+ Transketolase other sugars
NADPH and other enzymes

Glycolysis
Pyruvate Lactate
Pyruvate
dehydrogenase
Fatty acids Lipids
Acetyl-CoA
Amino acids Proteins

Acetylcholine Oxaloacetate
myelin
Citric acid
Citric acid
cycle

α-Ketoglutarate Thiamine-dependent enzymes

dehydrogenase
α-Ketoglutarate

Neurotransmitter
(e.g. glutamate)

FIGURE. Role of thiamine in various enzymatic pathways. CoA ¼ coenzyme A; NADPH ¼ nicotinamide
adenine dinucleotide phosphate.

hemorrhage, papilledema, anisocoria, or Korsakoff syndrome can present without ev-

miosis.2 It is suggested that the term
“ocular” should replace ophthalmoplegia in
the clinical triad.2 The third and final charac-
teristic is gait ataxia, the presentation of
which can range from mild gait abnormality
to a complete inability to stand.2 Addition-
ally, the presence of hypothermia, hypoten-
sion, and coma should increase the index
of suspicion for the disease.2 All the afore-
mentioned clinical findings are derived
from retrospective studies. Thus, in the
absence of large prospective data, the precise
prevalence of symptoms/signs of WE cannot
be determined. Approximately 80% of pa-
tients with untreated WE have development
of Korsakoff syndrome.8 Korsakoff syn-
drome consists of permanent memory
impairment associated with confabulation.8
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idence of acute signs and symptoms of WE.2
Other Clinical Manifestations Associated
With Thiamine Deficiency
Thiamine deficiency can also present as
other syndromes such as dry beriberi (neu-
ropathy), wet beriberi (neuropathy with
high-output congestive heart failure), gastro-
intestinal beriberi (abdominal pain, vomit-
ing, and lactic acidosis), and coma with
Marchiafava-Bignami disease.9,10 High-
output congestive heart failure, although
far less common than neuropathy, can pre-
sent with tachycardia, dyspnea on exertion,
electrocardiographic abnormalities, and
other symptoms. Peripheral edema may or
may not be a clinical feature in wet beriberi.2
Favorable outcome has been noted in such
1067

TABLE 1. Clinical Triad of Wernicke
Encephalopathy
1. Encephalopathy
d Disorientation
d Indifference
d Inattentiveness
d Decreased loss of consciousness
d Memory impairment
2. Oculomotor abnormalities
d Nystagmus
d Lateral rectus palsy
d Conjugate gaze palsy
d Internuclear ophthalmoplegia
d Unequal pupils
d Light-near dissociation
d Retinal hemorrhage
d Papilledema
3. Gait ataxia/cerebellar dysfunction
d Primarily stance and gait
d Unlike alcoholic cerebellar degeneration, Wernicke
encephalopathy has no upper limb ataxia
Other: Peripheral neuropathy, hypothermia,
hypotension, cardiac failure, coma
cases after thiamine replacement.11 Neuro-
pathic beriberi is a sensorimotor peripheral
neuropathy that often involves the lower ex-
tremities. It is painful and could result from
deficiency of multiple B vitamins, especially
pyridoxine and pantothenic acid.2,8 Notably,
patients receiving total parenteral nutrition
can present with components of all forms
of deficiency syndromes. In some of these
cases, the predominant presenting symptom
had been abdominal pain and lactic acidosis,
which can result in emergency exploratory
laparotomy with negative results.2
Diagnostic Challenges
WE often is undiagnosed until after death.
One autopsy study confirmed that WE was
suspected in only about one-third of alco-
holic and 6% of nonalcoholic patients during
their lifetime. This report could represent
extreme cases, and the number of patients
remaining undiagnosed before death is prob-
ably higher. These findings suggest that most
cases of WE are likely to remain unrecog-
nized and undiagnosed during life.12 It has
also been suggested autopsy should be
n n
1068 Mayo Clin Proc.
MAYO CLINIC PROCEEDINGS
performed in patients dying from symptoms
suggestive of WE for further clarification.12
The diagnosis of WE is primarily clinical,
yet the classic triad of memory impairments,
ophthalmoplegia, and cerebellar signs such
as gait ataxia are reported in only 10% of
the cases.7 In an attempt to reconsider diag-
nostic criteria for WE, Caine et al13 studied
the clinical features of 28 alcoholic patients
with autopsy-proven WE who were exten-
sively evaluated during life. They concluded
that in a cohort of known alcoholics, any 2
of the following 4 conditions should prompt
a presumptive diagnosis: (1) nutritional defi-
ciency, (2) ocular findings, (3) ataxia, and
(4) mental status changes. A case series
based on the criteria proposed by Caine
et al found that clinical features of WE could
vary significantly between alcohol-related
and nonealcohol-related etiologies. It was
noted that dietary deficiency and vomiting
were more frequent among nonalcoholics,
whereas eye and cerebellar signs were more
frequent among alcoholics.12 Also, the
classic triad was significantly more common
in alcoholics than in nonalcoholics. A
consensus guideline from the European
Federation of Neurological Societies recom-
mends that the clinical diagnosis of WE
should take into account the different pre-
sentations of clinical signs between alco-
holics and nonalcoholics and the higher
prevalence of the disease in alcoholics.12
Thiamine levels can be measured using
high-performance liquid chromatography.
The most commonly used method measures
free thiamine levels in plasma using high-
performance liquid chromatography; howev-
er, the result is not immediately available
and lacks sensitivity and specificity for diag-
nosing active disease. A less commonly used,
although more accurate, method involves
detecting monophosphorylated and diphos-
phorylated thiamine in whole red blood cells
given that the majority of the blood’s thia-
mine is present in such cells.14 Even though
laboratory assay is not diagnostic for WE, it
can identify patients with very low circu-
lating levels of thiamine who are at risk of
development of WE. Thiamine assay is
important in cases of ambiguous
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THIAMINE DEFICIENCY AND WERNICKE ENCEPHALOPATHY
presentation and can be measured before
administration of thiamine.2
In terms of imaging, computed tomogra-
phy is not a reliable test for WE.12 Conven-
tional magnetic resonance imaging (MRI)
performs better and can identify WE-
related lesions in two-thirds of patients.12
Areas of increased T2 and fluid-attenuated
inversion recovery signals, decreased T1
signal, and diffusion abnormality surround-
ing the aqueduct and third ventricle and
within the medial thalamus, dorsal medulla,
tectal plate, and mammillary bodies can be
typically identified on the MRI. Involvement
of corpus callosum on MRI should raise sus-
picion for Marchiafava-Bignami disease, a
rare disorder seen in people with chronic
alcohol consumption and malnutrition due
to vitamin B complex deficiencies. It can pre-
sent in a similar fashion as WE and should
be considered in the differential diagnosis.15
However, performing MRI on an emergent
basis for this indication is cumbersome.
Overall, thiamine administration, either in
high or low dosage, is considered low risk
and untreated patients could have serious
adverse consequences. Thus, any form of
diagnostic testing (either laboratory or diag-
nostic imaging) should not delay treatment
in individuals suspected of having WE.16
Caveats
Other medical conditions (Table 2) such as
stroke, drug overdose, other encephalopa-
thies, and infections such as meningitis
could mimic WE. These disorders should
be thoroughly evaluated, particularly in pa-
tients at low risk for WE.2 Conversely, WE
can be precipitated in high-risk patients
such as those with critical illness or sepsis
due to increased metabolic demand causing
relative thiamine deficiency. In patients
with cancer, absolute thiamine deficiency
can occur because of malabsorption, malnu-
trition, or vomiting, triggering WE.6-8,17
In patients with eating disorders such as
anorexia nervosa (AN), self-imposed long-
term nutritional deprivation can lead to thia-
mine deficiency. Individuals who have rapid
weight loss are particularly vulnerable to
development of WE.18 Additionally, there
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TABLE 2. Diagnostic Mimics of Wernicke
Encephalopathy
1. Drugs and toxins
d Prescription medications (eg, opioids, sedative-
hypnotics, antipsychotics, lithium, skeletal muscle
relaxers, polypharmacy)
d Nonprescription medications (eg, antihistamines)
d Drugs of abuse (eg, ethanol, heroin, hallucinogens,
nonmedicinal use of prescription medications)
d Withdrawal states (eg, ethanol, benzodiazepines)
2. Medication adverse effects (eg, hyperammonemia
from valproic acid, confusion from quinolones,
serotonin syndrome)
3. Sepsis/infection
4. Metabolic derangements
d Electrolyte disturbance (elevated or depressed): so-
dium, calcium, magnesium, phosphate
d Endocrine disturbance (depressed or increased):
thyroid, parathyroid, pancreas, pituitary, adrenal
d Hyperglycemia and hypoglycemia
d Hyperosmolar and hypo-osmolar states
d Hypercarbia and hypoxia
d Inborn errors of metabolism: porphyria, Wilson
disease
5. Brain disorders
d Central nervous system infection
d Seizures, especially nonconvulsive status epilepticus
d Head trauma
d Hypertensive encephalopathy
d Psychiatric conditions
6. System organ failure
d Cardiac, kidney, and liver failure
is considerable comorbidity between eating
disorders and substance use disorders. The
subgroup of patients with AN and alcohol
use disorders is at higher risk of develop-
ment of WE.19 Patients who have undergone
bariatric surgery are another group at risk of
development of WE due to thiamine malab-
sorption and greater incidence of alcohol
abuse among such patients.20 Patients with
AN and alcohol use disorders should be
referred to specialty care for evidence-based
evaluation and treatment recommendation.
Treatment
The mainstay of treatment is administration
of thiamine in a timely fashion. Diagnostic
confirmation is often difficult and delayed,
1069

and therefore a high degree of clinical suspi-
cion and recognition of disease should
prompt the clinician to initiate treatment at
the earliest opportunity. This practice is
based on opinion that thiamine is relatively
inexpensive and safe, and its quick adminis-
tration has been reported to prevent progres-
sion of WE to irreversible deficits of
Korsakoff syndrome.21
However, there is no consensus on the
effective dose of thiamine, route of adminis-
tration, daily dose frequency, or the duration
of the treatment. The traditional recommen-
dation is a parenteral thiamine dosage of 100
mg/d.8 This recommendation is not based on
controlled trials. Some reports argue that
dosages higher than 100 mg are required
for the treatment of WE, especially in alco-
holics.7,8,22 Chronic alcohol users are
susceptible to poor nutritional intake,
gastrointestinal malabsorption, and reduced
hepatic reserve. It is logical that alcoholics
will require a higher daily dosage of thia-
mine. High-dose parenteral administration
will also facilitate better passive diffusion of
thiamine across the blood-brain barrier.23
In terms of parenteral administration, the
intravenous route is preferred over intra-
muscular.2 Pharmacokinetic studies have
documented that the plasma half-life of thia-
mine is only 96 minutes.24 Thus, adminis-
tering thiamine 2 to 3 times daily might
achieve better bioavailability than a single
dose. Adverse reactions to thiamine are
rare. As such, thiamine is very well tolerated
regardless of the route of administration or
dosage form.2 The European Federation of
Neurological Societies guideline recom-
mends intravenous infusion of thiamine,
200 mg diluted with 100 mL of normal sa-
line or 5% dextrose, given over 30 minutes
3 times daily in cases of WE.12 In nutrition-
ally deficient patients, thiamine should be
administered before glucose to avoid iatro-
genic occurrence of WE. Because magne-
sium serves as a cofactor for thiamine
activity, its level should also be checked
and be supplemented via oral or parenteral
administration in cases of hypomagnese-
mia.5 Hospital admission is recommended
for the management of acute WE, which
n n
1070 Mayo Clin Proc.
MAYO CLINIC PROCEEDINGS
will require parenteral administration of
thiamine.2 Patients with nonacute WE will
receive prophylactic oral thiamine in the
outpatient setting.2 Education on the adverse
consequences of thiamine deficiency should
be incorporated into the treatment plan.
Prevention
Oral administration of thiamine at 100 mg 3
times daily may be reserved for patients with
low suspicion of deficiency for prophylaxis
or after correction through parenteral
administration. This treatment is based on
standard clinical practice because insuffi-
cient evidence exists in the literature to sup-
port this recommendation. Another mode of
WE prevention has been studied in
Australia, where the incorporation of thia-
mine to bread flour was found to decrease
the prevalence of WE in a prospective au-
topsy study.25 This practice has been adop-
ted by many other Western countries
where food is fortified with thiamine and
other essential vitamins.
Does Treatment Work?
Thiamine administration can improve symp-
toms to a certain extent, especially if admin-
istered promptly. Ocular findings respond
well to treatment. The response to thiamine
administration on ocular findings is quite
predictable and constant. Failure of recovery
should alert the physician to consider alter-
native diagnoses. In most cases, horizontal
and vertical gaze palsies and ptosis recover
completely within days to weeks. Although
horizontal nystagmus shows dramatic recov-
ery soon after treatment with thiamine, it
can persist in a subtle manner for months
in up to 60% of the patients.21
Delayed recovery is seen in gait ataxia in
contrast to ocular signs and symptoms. Some
patients experience complete improvement,
although most are left with residual gait dis-
turbances. In patients with chronic dementia
of unclear reason, fine horizontal nystagmus
and gait abnormalities can be clues to
alcohol-related etiology.21
Mental status changes and acute enceph-
alopathy often gradually recede, but residual
neurologic deficits are common and
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THIAMINE DEFICIENCY AND WERNICKE ENCEPHALOPATHY
persistent.2 Mild neurocognitive symptoms
such as apathy, drowsiness, and confusion
respond well to treatment. Memory and
learning deficits, on the other hand, show
poor recovery, and unfortunately, many
patients are left with permanent residual
Korsakoff amnesia.
CONCLUSION
Wernicke encephalopathy is a medical emer-
gency that is poorly understood and underre-
cognized. Although most prevalent in
patients with alcohol use disorders, anyone
who has a nutritional deficiency of thiamine
is at high risk for development of WE. A
high index of suspicion should be maintained
in specific patient cohorts such those with ma-
lignant diseases or eating disorders and those
who have undergone bariatric surgery. The
classic clinical triad of the syndrome consist-
ing of altered mental status, eye movement
disorders, and gait ataxia may be present in
only 10% of cases. Absence of the classic triad
in initial presentation often leads to underdi-
agnosis. Thus, the syndrome is most often
recognized only on autopsy. Pursuing a high
index of suspicion is recommended in vulner-
able populations because treatment has the
potential to reverse the neuropsychiatric syn-
drome. Treatment consists of timely adminis-
tration of thiamine. No randomized,
controlled clinical trials of treatment exist.
Consensus guidelines support parenteral
administration, preferably through an intra-
venous route to rapidly restore serum concen-
trations with concerns of gastrointestinal
malabsorption that occurs in patients with
alcohol use disorder and other conditions
associated with thiamine deficiency. Prompt
recognition and treatment of WE should be
exercised by all primary care and emergency
room physicians.
ACKNOWLEDGMENTS
All authors are accountable for all aspects of
the work and agreed to submission of the
manuscript to Mayo Clinic Proceedings. Spe-
cific areas of contribution are as follows: Shir-
shendu Sinhadconception, design, and
drafting of work, revising for important
Mayo Clin Proc. n June 2019;94(6):1065-1072 n https://doi.org/10.1016/j.mayocp.2019.02.018
www.mayoclinicproceedings.org
intellectual content; Archish Katariad
design, drafting of work, revising for impor-
tant intellectual content; Bhanu Prakash
Kolladrevising for important intellectual
content; Nuria Thusiusdrevising for
important intellectual content; Larissa
Loukianovadapproval of the version to be
published.
Abbreviations and Acronyms: AN = anorexia nervosa;
MRI = magnetic resonance imaging; WE = Wernicke
encephalopathy
Potential Competing Interests: Dr Sinha has received
grant funding from UCare. The other authors report no
competing interests.
Correspondence: Address to Shirshendu Sinha, MBBS,
Department of Psychiatry and Psychology, Mayo Clinic
Health SystemeSouthwest Minnesota Region, 101 Martin
Luther King Jr Dr, Mankato, MN 56001 (sinha.shirshendu@
mayo.edu).
REFERENCES
1. Torvik A. Wernicke’s encephalopathydprevalence and clinical
spectrum. Alcohol Alcohol Suppl. 1991;1:381-384.
2. Donnino MW, Vega J, Miller J, Walsh M. Myths and misconcep-
tions of Wernicke’s encephalopathy: what every emergency
physician should know. Ann Emerg Med. 2007;50(6):715-721.
3. Vasconcelos MM, Silva KP, Vidal G, Silva AF, Domingues RC,
Berditchevsky CR. Early diagnosis of pediatric Wernicke’s en-
cephalopathy. Pediatr Neurol. 1999;20(4):289-294.
4. Harrigan GG, Maguire G, Boros L. Metabolomics in alcohol research
and drug development. Alcohol Res Health. 2008;31(1):26-35.
5. Thomson AD, Cook CC, Touquet R, Henry JA; Royal College
of Physicians, London. The Royal College of Physicians report
on alcohol: guidelines for managing Wernicke’s encephalopathy
in the Accident and Emergency department [published correc-
tion appears in Alcohol Alcohol. 2003;38(3):291]. Alcohol Alcohol.
2002;37(6):513-521.
6. Charness ME, DeLaPaz RL. Mamillary body atrophy in Wer-
nicke’s encephalopathy: antemortem identification using mag-
netic resonance imaging. Ann Neurol. 1987;22(5):595-600.
7. Harper CG, Giles M, Finlay-Jones R. Clinical signs in the
Wernicke-Korsakoff complex: a retrospective analysis of 131
cases diagnosed at necropsy. J Neurol Neurosurg Psychiatry.
1986;49(4):341-345.
8. Victor M, Adams RD, Collins GH. The Wernicke-Korsakoff Syn-
drome and Related Neurologic Disorders Due to Alcoholism and
Malnutrition. 2nd ed. Philadelphia, PA: FA Davis; 1989.
9. Campbell CH. The severe lacticacidosis of thiamine deficiency:
acute pernicious or fulminating beriberi. Lancet. 1984;2(8400):
446-449.
10. Hillbom M, Pyhtinen J, Pylvänen V, Sotaniemi K. Pregnant, vom-
iting, and coma. Lancet. 1999;353(9164):1584.
11. Shimon I, Almog S, Vered Z, et al. Improved left ventricular
function after thiamine supplementation in patients with
congestive heart failure receiving long-term furosemide therapy.
Am J Med. 1995;98(5):485-490.
12. Galvin R, Bråthen G, Ivashynka A, Hillbom M, Tanasescu R,
Leone MA. EFNS guidelines for diagnosis, therapy and preven-
tion of Wernicke encephalopathy. Eur J Neurol. 2010;17(12):
1408-1418.
1071

13. Caine D, Halliday GM, Kril JJ, Harper CG. Operational criteria
for the classification of chronic alcoholics: identification of Wer-
nicke’s encephalopathy. J Neurol Neurosurg Psychiatry. 1997;
62(1):51-60.
14. Mayo Clinic Laboratories. Thiamine (Vitamin B1), Whole
Blood. Mayo Clinic Laboratories website. https://www.
mayocliniclabs.com/test-catalog/ClinicalþandþInterpretive/42356.
Accessed April 26, 2019.
15. Fernandes LMP, Bezerra FR, Monteiro MC, et al. Thiamine defi-
ciency, oxidative metabolic pathways and ethanol-induced
neurotoxicity: how poor nutrition contributes to the alcoholic
syndrome, as Marchiafava-Bignami disease. Eur J Clin Nutr. 2017;
71(5):580-586.
16. Kaineg B, Hudgins PA. Wernicke’s encephalopathy [images in
clinical medicine]. N Engl J Med. 2005;352(19):e18.
17. Isenberg-Grzeda E, Shen MJ, Alici Y, Wills J, Nelson C,
Breitbart W. High rate of thiamine deficiency among inpa-
tients with cancer referred for psychiatric consultation: results
of a single site prevalence study. Psychooncology. 2017;26(9):
1384-1389.
18. Oudman E, Wijnia JW, Oey MJ, van Dam MJ, Postma A.
Preventing Wernicke’s encephalopathy in anorexia nerv-
osa: a systemic review. Psychiatry Clin Neurosci. 2018;
72(10):774-779.
n n
1072 Mayo Clin Proc. June 2019;94(6):1065-1072
MAYO CLINIC PROCEEDINGS
19. Bulik CM, Klump KL, Thornton L, et al. Alcohol use disorder co-
morbidity in eating disorders: a multicenter study. J Clin Psychi-
atry. 2004;65(7):1000-1006.
20. Oudman E, Wijnia JW, van Dam M, Biter LU, Postma A. Pre-
venting Wernicke encephalopathy after bariatric surgery. Obes
Surg. 2018;28(7):2060-2068.
21. Ropper AH, Samuels MA, Klein JP. Diseases of the nervous system
caused by nutritional deficiency. In: Ropper AH, Samuels MA,
Klein JP, eds. Adams and Victor’s Principles of Neurology. 10th ed.
New York, NY: McGraw-Hill; 2014:1161-1185.
22. Chataway J, Hardman E. Thiamine in Wernicke’s syndro-
medhow much and how long [letter]? Postgrad Med J. 1995;
71(834):249.
23. Thomson AD, Guerrini I, Marshall EJ. The evolution and treat-
ment of Korsakoff’s syndrome: out of sight, out of mind? Neuro-
psychol Rev. 2012;22(2):81-92.
24. Tallaksen CM, Sande A, Bøhmer T, Bell H, Karlsen J. Kinetics of
thiamin and thiamin phosphate esters in human blood, plasma
and urine after 50 mg intravenously or orally. Eur J Clin Pharma-
col. 1993;44(1):73-78.
25. Harper CG, Sheedy DL, Lara AI, Garrick TM, Hilton JM,
Raisanen J. Prevalence of Wernicke-Korsakoff syndrome in
Australia: has thiamine fortification made difference? Med J
Aust. 1998;168(11):542-545.
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