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Malaysian Journal of Medical Sciences
School of Medical Sciences, Universiti Sains Malaysia
ISSN: 1394-195X
Vol. 9, Num. 2, 2002, pp. 43-46
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Malaysian Journal of Medical Sciences, Vol. 9, No. 2, July 2002, pp. 43-46
Wernicke's Encephalopthy associated
with hyperemesis gravidarum - A CASE REPORT
Wahinuddin Sulaiman, Azerin Othman, Monniaty Mohamad, Hj. Rosemi
Salleh, Lily Mushahar
Department of Medicine, Hospital Kota Bharu,
15586 Kota Bharu, Kelantan, Malaysia.
Correspondence: Dr. Wahinuddin Sulaiman Department
of Medicine, Hospital Taiping, 34000, Taiping, Perak.
Submitted-20.2.2001
Revised-14.6.2001
Accepted-24.6.2001
Code Number: mj02016
Two cases of Wernicke's encephalopathy due to hyperemesis
gravidarum are described. The first patient presented with bilateral papilloedema,
altered sensorium and the second with bilateral retinal haemorrhages, ophthalmoplegia
and nystagmus. Both patients were diagnosed with Wernicke's encephalopathy
on clinical ground since there were no laboratory facilities to measure red
cell transketolase and thiamine pyrophosphate levels. This is a rare but treatable
complication of hyperemesis gravidarum (HG) and due to lack of diagnostic tools,
there is often diagnostic uncertainty, delay in commencing appropriate treatment,
as well as irreversible damage to the upper brain stem and death.
Key words : Wernicke's encephalopathy, hyperemesis
gravidarum
INTRODUCTION
Wernicke's encephalopathy is usually associated with chronic
alcoholism(1). Hyperemesis gravidarum is one of many other causes of Wernicke's
encephalopathy in clinical practice (2,3). Other causes include undernutrition,
starvation, anorexia, intravenous feeding (2,3), and chemotherapy. It may be
precipitated by glucose administration to patients especially those with thiamine
deficiency.
We report 2 cases of severe Wernicke's encephalopathy where
the presence of papilloedema resulted in the delay in diagnosis and unfortunately
death in the first case, and severe coagulopathy with respiratory failure requiring
ventilatory support in the second.
Case report
Case 1
A 42-year old housewife presented in the 16th week of her
fifth pregnancy. Her previous
pregnancies were uneventful. She denied history
of alcohol consumption. She was treated as hyperemesis gravidarum because she
had been vomiting for 8 weeks continuously despite
various antiemetics. At 16 weeks of gestation she
became drowsy and unresponsive to call with
impaired hearing and vision. Further history obtained
revealed that she also had unsteadiness of gait few days
prior to admission.
On admission, she was drowsy and unable to obey simple commands.
There was intermittent right facial muscle twitching. However, she moved all
four limbs on pain stimuli. She had a diffuse goitre but was clinically euthyroid.
There was neither meningism nor cerebellar signs. The reflexes were normal
with negative Babinski response. Fundoscopy showed bilateral papilloedema with
multiple haemorrhagic spots. Her blood pressure was 170/100 mmHg.
Based on the clinical findings, she was diagnosed as having
encephalitis with a differential diagnosis of cerebral sagittal sinus thrombosis.
Computer tomographic (CCT) scan of the brain was normal. Magnetic Resonance
Imaging (MRI) was deferred in view of patient's clinical instability.
Echocardiography showed no clot in the cardiac chambers, and
no structural or functional abnormality. She had a deranged coagulation profile
suggestive of early disseminated intravascular coagulopahty. Other laboratory
investigations (collagen screening, blood counts, septic screening, viral serology)
were unremarkable. Lumbar puncture was suggested but refused by the patient's
family.
She was ventilated and a diagnosis of Wernicke's encephalopathy
was made by clinical and laboratory exclusion of other possible differential
diagnoses and was given intravenous thiamine. Unfortunately, she could not
be weaned off ventilatory support and despite high dose thiamine and other
supportive measures, she succumbed to the illness and died 4 days after admission.
Case 2.
A 25-year old gravida two Malay lady, who was twelve weeks
pregnant was admitted to Hospital Kota Bharu following a week's history of
giddiness and unsteady gait with blurring of vision. She was hospitalised earlier
at a district hospital for hyperemesis gravidarum at eight weeks of gestation
for a month. She was given antiemetics but no vitamins. She was otherwise premorbidly
well and healthy.
Throughout her hospitalisation at the district hospital, she
was given intravenous dextrose and saline. On admission she was noted to have
slow mentation, but able to follow commands, apyrexic, with stable vital signs.
Nystagmus was present in both vertical and horizontal direction but the range
of eye movement were full. The pupils were reactive. There was flame shape
haemorrhages in both fundi but no papilloedema. She moved all limbs spontaneously
but was unable to cooperate to test the gait. Sensation was intact and cerebellar
signs absent. Clinically she had no goitre.
A clinical diagnosis of Wernicke's encephalopathy was made
after excluding other possibilities such as systemic lupus erythematosus, by
laboratory investigations (serum C3 and C4, and antinuclear
antibody). However, she had a prolonged International Normalised Ratio (INR)
and raised free T4 (59.16 nmol/L), free T3 (6.98 nmol/L) with a low serum TSH
levels (< 0.03 mU/L), which suggested thyrotoxicosis. CT scan of the brain
was normal. She was treated with high dose intravenous thiamine 300 mg daily,
propylthiouracil and
methylprednisolone. She had a
spontaneous abortion a week after admission. Following
the administration of thiamine, she made a great improvement in her neurological
function within a month in the ward. Her mentation and memory gradually improved.
She was allowed to go
home with close supervision by her family members.
She was advised to continue the oral thiamine until
she regained her normal function. During her assessment in the outpatient clinic
at 8 weeks after discharge, she managed to resume her daily
activities although still not ambulating well due to
residual weakness of both lower limbs and she was
clinically and biochemically euthyroid.
DISCUSSION
Wernicke's encephalopathy (WE) was first described by Carl
Wernicke in 1881 as a classical triad of acute mental confusion, ataxia and
ophthalmoplegia and was first reported in 1914 as a complication of hyperemesis
gravidarum and subsequently increasing number of cases have been reported (4
- 12). Wernicke's encephalopathy is a consequence of thiamine (vitamin B1)
deficiency which is essential for carbohydrate metabolism and can be fatal
if not treated. It was previously believed that WE is commonly associated with
alcoholism (1). Nevertheless, it also should be considered in patients with
anorexia nervosa (13), prolonged vomiting associated with chemotherapy, elderly
patients living alone, gastrointestinal disease, peritoneal dialysis and haemodialysis
(14) and human immunodeficiency virus infection. It can be precipitated in
the hospital by glucose administration to patients with thiamine deficiency.
Due to its rarity, especially among the Malay race of Muslim
religion in this part of the country where alcohol is forbidden, Wernicke's
encephalopathy may not carry a high index of suspicion. Wernicke's encephalopathy
is still an uncommon complication of hyperemesis gravidarum, which is fairly
common.
We believe that both our patients with a background history
of severe and prolonged hyperemesis gravidarum eventually developed Wernicke's
encephalopathy.
Diagnostic uncertainty led to the delay in appropriate treatment
to our first patient who eventually succumbed and died. Although the presentation
may not be so obvious and the classical triad of Wernicke's encephalopathy
was not present, the combination of hyperemesis gravidarum and
neurological manifestations i.e. visual blurring
and unsteadiness of gait, papilloedema with
retinal haemorrhages prompted us to make the
diagnosis of Wernicke's encephalopahty, albeit too late.
However, Wernicke's encephalopathy was well illustrated in
the second patient. The immediate replacement with high dose parenteral thiamine
and other supportive measures, including ventilatory support, gradually improved
her symptoms.
Papilloedema has not been described as an associated physical
sign in a large retrospective study (15) and it is a rare finding as reported
in previous analyses (4). Retinal haemorrhages, however, has been found to
be a more frequent manifestation (16) of Wernicke's encephalopathy. The pathophysiology
of papilloedema in Wernicke's encephalopathy is still unclear. As in our cases,
both had retinal haemorrhages and the first patient had papilloedema, for which
there was no evidence to suggest increased intracranial pressure as showed
by normal brain CT.
There have been case reports of gestational thyrotoxicosis
associated with hyperemesis gravidarum manifesting as Wernicke's encephalopathy
(17,18). As shown in the second patient, thyrotoxicosis was diagnosed based
on the biochemical result. The cause of the thyrotoxicosis has previously been
identified to be closely associated with human chorionic gonadotropin (hCG).
Both the thyrotoxicosis and a catabolic state due to the hyperemesis were thought
to induce B1 deficiency, causing Wernicke's encephalopathy.
Although, in our second case, thyroid storm may not be disputed,
the clinical finding was much less milder than those expected for hyperthyroid
Graves' disease. Corticosteroid have shown to have beneficial effect on Wernicke's
encephalopathy (19).
The red cell transketolase and thiamine pyrophosphate activities
will help to support the clinical diagnosis of Wernicke's encephalopathy. However,
one should not await the result of this assay if Wernicke's encephalopathy
is highly suspected and thus administration of thiamine should not be delayed.
These supportive investigations however, are not available in our laboratory.
MRI of the brain should be done when investigating for Wernicke's encephalopathy
as reported in previous analyses (20,21,22). The MRI of the brain will show
increased T2 weighted signal intensity in various areas such as the mamillary
bodies, paraventricular regions of the thalamus and in periaqueductal regions
of the midbrain. However, the MRI findings in our second patient was unremarkable.
Our present cases illustrate the importance of knowing that
Wernicke's encephalopathy may complicate clinical conditions that deplete thiamine
and that all patients with prolonged vomiting of any cause including hyperemesis
gravidarum with poor nutritional status and impaired conscious level should
be treated with high dose parenteral thiamine, whether the classical features
of Wernicke's encephalopathy are present or not. In both cases, the diagnosis
can not be 100 % verified as MRI was not available in the first case and other
differential diagnosis need to be considered. One should also consider other
intracranial pathologies which may cause papilloedema, which is infrequently
associated with Wernicke's encephalopathy, and the administration of thiamine
should not be delayed just because of the presence of papilloedema. These two
cases illustrates that the diagnosis of Wernicke's encephalopathy should be
high in the list of differential diagnoses in patient with hyperemesis gravidarum
presenting with clinical features of
upper brainstem signs.
ACKNOWLEDGEMENT
I would like convey many thanks to Professor Dr. Eddy Nyunt
Win, Consultant Neurologist/Head of Department of Medicine, International Medical
University for his tremendous encouragement, advise and editing this report.
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Copyright 2002 - Malaysian Journal of Medical Sciences
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