Clinical Neurology and Neurosurgery 113 (2011) 490–492

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Clinical Neurology and Neurosurgery
journal homepage: www.elsevier.com/locate/clineuro

Case report

Wernicke’s encephalopathy due to hyperemesis gravidarum . . . and fetal stroke:
What relationship?
Damien Biotti a,∗ , Guy-Victor Osseby a,1 , Christine Durand b , Bernard Lorcerie c ,
Stephanie Couvreur d , Thibault Moreau a,1 , Maurice Giroud a,1
a

Neurology Department, General Hospital, University Hospital, 21000 Dijon, France
Radiology Department, General Hospital, University Hospital, 21000 Dijon, France
Internal Medicine Department, General Hospital, University Hospital, 21000 Dijon, France
d
Obstetrical Department, University Hospital, 21000 Dijon, France
b
c

a r t i c l e

i n f o

Article history:
Received 24 May 2009
Received in revised form
22 November 2010
Accepted 24 January 2011
Available online 5 March 2011
Keywords:
Hyperemesis gravidarum
Wernicke encephalopathy
Thiamine/therapeutic use
Pregnancy
Neonatal stroke

1. Introduction
Wernicke’s encephalopathy is a form of encephalopathy resulting from thiamine (vitamin B1) deficiency. It is a classical evolution,
but fortunately, today, it occurs rarely in a context of hyperemesis
gravidarum. When it does occur, however, there is a high risk of
complications for the fetus. We report here the case of a patient
who presented this syndrome, and whose fetus suffered ischemic
stroke. We discuss the characteristics of this syndrome in the context of pregnancy and the associations between maternal and fetal
disorders.
2. Case report
The patient was a 30-year-old woman in the 19th week of her
second pregnancy. She was referred to our neurology department
for a confusional syndrome with cerebellar ataxia and nystagmus
that had lasted 72 h. The patient had a medical history of deep
venous thrombosis complicated by pulmonary embolism in 2001
and again in 2003 during her first pregnancy. None of the examina-

∗ Corresponding author. Tel.: +33 380293753; fax: +33 3 80 29 36 72.
1

E-mail address: dbiotti@hotmail.com (D. Biotti).
Tel.: +33 633785331.

0303-8467/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.clineuro.2011.01.007

tions for thrombophilia were abnormal. During the first pregnancy,
the patient had already suffered from uncontrollable vomiting for
the first 16 weeks, which led to a weight loss of 15 kg; she also
suffered from hyperthyroidism treated with propylthiouracile.
The vomiting in the present case started when the pregnancy
was discovered. It was incapacitating, did not respond to symptomatic treatment and, as a result, the patient was hospitalized
several times for short periods. The patient was finally provided
with medical care at home. Because of the vomiting and the
patient’s refusal to have a naso-gastric tube, she was rehydrated
intravenously with a fluid containing glucose but not enriched with
vitamins.
Five days before her admission the patient developed confusional syndrome and cerebellar ataxia diagnosed by the
patient’s G.P., who immediately transferred her to the neurology
department. The patient was apyretic, presented temporospatial
disorientation with incoherent speech. Because of severe cerebellar
ataxia, the patient was unable to stand. We noticed multidirectional
nystagmus. The rest of the clinical examination was normal. Wernicke’s encephalopathy was suspected and the patient was treated
intravenously with 1 g/d of vitamin B1.
The diagnosis was quickly confirmed by the extremely low
levels of vitamin B1: erythrocyte transketolase activity was 1.35
(normal range 1.00–1.09), the thiamine pyrophosphate effect was
30 (normal range 80–165 ng/mL), and by brain MRI which revealed

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491

Fig. 1. Axial (A, B and C) and sagittal (D) FLAIR T2-weighted images of the brain revealing abnormal mammillary bodies and periaqueductal grey matter hyperintensities.

hyperintensity in FLAIR/T2-Weighted images of the mammillary
bodies and the periaqueductal grey matter, which is strongly associated with this syndrome (Fig. 1). For other vitamins, analysis
showed deficiencies in vitamins B6, D and K. Analysis of thyroid function showed hyperthyroidism with low levels of TSH
(0.020 mUI/L (0.360–3.740 mUI/L)) and an increase in T4 hormone
(24.5 pmol/L (9.8–18.8 pmol/L)). Levels of thyroid peroxidase, thyroglobulin and TSH-receptor antibodies were insignificant.
MRI of the fetal brain performed as soon as the patient had been
admitted revealed infarction of the right cerebral hemisphere and
a large edema suggesting a recent stroke which compressed the
foramina of Monro causing secondary porencephaly under pressure
(Fig. 2). Fetal ultrasonography confirmed these findings with structures deviated from the midline. The biological examination was
negative for infection, inflammation and thrombophilia (platelets,
fibrinogen, homocysteine, antithrombin III, proteins C and S, activated protein C resistance, factor V Leiden, prothrombin mutation,
lupus anticoagulants, anticardiolipin antibody and anti␤2 glycoprotein 1 antibody).
After several days of treatment, the cerebellar ataxia and the
nystagmus improved, but the patient’s condition evolved towards
Korsakoff syndrome. The pregnancy had to be terminated and
pathological examination of the fetus confirmed that the stroke was
ischemic induced by occlusion of the homolateral carotid artery
and affected the whole of the right hemisphere. Several areas of
hemorrhagic transformation were also seen.
3. Discussion
Wernicke’s encephalopathy is a classical, but fortunately rare
complication of hyperemesis gravidarum. The condition is far more
frequent in alcoholism-related deficiency. The association of this

syndrome with concomitant fetal stroke as found in our patient is
exceptional.
Wernicke’s encephalopathy is a neurological and metabolic consequence of thiamine (vitamin B1) deficiency. Its prevalence is
difficult to evaluate as it is probably underdiagnosed. Nevertheless, Harper et al. [1] estimated a prevalence between 0.4 and 1.4%
in France. The classical clinical triad is an association of cerebellar
ataxia, oculomotor disturbances, especially nystagmus, and confusional syndrome. This triad is classical, but not always present and
may be completely absent. Wernicke’s encephalopathy has been
reported in up to 20% of cases in autopsy series, which shows that
in a high proportion of cases, the disease was not diagnosed when
the patient was alive [2]. Brain MRI is the complementary examination of choice and reveals symmetrical bilateral hyperintensity
on T2-Weighted images of the mammillary bodies, the thalamus,
the periventricular region of V3 and V4 and the periaqueductal grey
matter.
The stock of thiamine in the body will last for a maximum of 2–3
weeks, which explains the rapid and unexpected onset of this syndrome in predisposing conditions, in particular in cases of chronic
alcoholism, insufficient intake, impaired absorption or hypermetabolism [2]. Without treatment the syndrome results in the death
of the patient in 17% of cases or frequently leads to Korsakoff syndrome [2]. Early diagnosis and the emergency implementation of
treatment with parenteral vitamin B1 are therefore essential.
Vomiting and nausea, related to Human Chorionic Gonadotropin
(hCG) levels, are very frequent in the early weeks of pregnancy.
Hyperemesis gravidarum occurs in 0.3–1% of pregnancies [3] and
is the pathological form of the condition with severe, long-lasting
and uncontrollable vomiting, which often requires periods of hospitalization. It is also the cause of many complications principally
metabolic in nature. This pathology most often appears at the

Fig. 2. T2-weighted images of the fetus. In the brain we observed an aspect of large porencephaly under pressure; the maximum ventricular dilatation measured 31 mm.
The right hemispheric structures had almost completely disappeared with a mass effect and deviation of the midline structures to the left.

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D. Biotti et al. / Clinical Neurology and Neurosurgery 113 (2011) 490–492

beginning of the pregnancy and is frequently associated with a
history of psychiatric, digestive or endocrine disorders; recurrence during the second pregnancy is seen in around 15% of
cases. Hyperemesis gravidarum is associated with considerable
morbi-mortality; Wernicke’s encephalopathy is the principal complication in motherhood and responsible for up to 50% of fetal
deaths via direct or indirect mechanisms [4]. Fetal loss could even
be the first sign of Wernicke’s encephalopathy. Chiossi et al. [4]
showed that on average Wernicke’s encephalopathy occurred after
7 weeks of vomiting and in around the 14th week of pregnancy.
Moreover, pregnancy is a high-risk period for thiamine deficiency
because of the hypermetabolism induced by the pregnancy and
because of the risk of vomiting and digestive disturbances that may
increase vitamin losses and reduce intake. Hypermetabolism due to
physiological pregnancy-related hyperthyroidism may also evolve
towards another risk factor, true thyrotoxicosis. Certain series of
hyperemesis gravidarum report up to 2/3 of patients with associated hyperthyroidism, as was the case in our patient [5]. Apart from
cases of auto-immune hyperthyroidism, which may also be seen,
the most frequently reported mechanism able to explain hyperthyroidism is a cross-reaction between hCG and thyrotropin, which
induces stimulation of the thyroid gland [3].
The second point of interest is the possible consequence of
maternal Wernicke’s encephalopathy on the fetal brain. No data
are available in the literature. We know that high fetal mortality
is described but there are no specific explanations on the possible
increased risk of hemorrhagic or ischemic fetal stroke. In our case,
we found right hemisphere infarction on the fetal brain MRI. It is
tempting to try to establish a link between the mother’s condition
and that of the fetus. Indeed, even though it was difficult to date
the stroke, the fact the patient could no longer feel her baby moving
could suggest that the stroke had occurred shortly before.
Finally, the management of hyperemesis gravidarum is essential. A recent review of the literature [3] underlined the interest of

dietary hygiene, such as modifications in diet (certain foods may
trigger vomiting), in the mildest forms of the disease or the use of
relaxation techniques. Nevertheless, in the more severe cases more
stringent measures including hospitalization may be required. Oral
and sometimes parenteral nutrition and rehydration are necessary
to improve the clinical status of the mother and fetus, in which
case glucose solutions should be avoided as they may trigger the
onset of Wernicke’s encephalopathy. Finally, antiemetics may be
used as they are effective, safe and are associated with reduced
fetal morbidity.
Suspected Wernicke’s encephalopathy is a medical emergency.
Oral supplementation is no longer indicated and the intravenous or
intramuscular route must be used. There is no consensus regarding
the duration of treatment or the recommended daily dose [2].
4. Conclusion
We report the case of a patient with Wernicke’s encephalopathy in the context of hyperemesis gravidarum in whom imaging
unexpectedly revealed concomitant fetal stroke thus raising the
possibility of a relationship between these two cerebral diseases.
References
[1] Harper C, Fornes P, Duyckaerts C, Lecomte D, Hauw JJ. An international perspective on the prevalence of the Wernicke-Korsakoff syndrome. Metab Brain Dis
1995;10:17–24.
[2] Sechi G, Serra A. Wernicke’s encephalopathy: new clinical settings and recent
advances in diagnosis and management. Lancet Neurol 2007;6:442–55.
[3] Niebyl JR, Clinical practice. Nausea and vomiting in pregnancy. N Engl J Med
2010;363:1544–50.
[4] Chiossi G, Neri I, Cavazzuti M, Basso G, Facchinetti F. Hyperemesis gravidarum
complicated by Wernicke encephalopathy: background, case report, and review
of the literature. Obstet Gynecol Surv 2006;61:255–68.
[5] Gartner R. Thyroid disorders during pregnancy. Deutsche medizinische Wochenschrift 2009;134:83–6 (1946).