An unusual case of Wernicke's encephalopathy with intrauterine fetal death following hyperemesis gravidarum
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.190268
Source of Support: None, Conflict of Interest: None
Wernicke's encephalopathy (WE) is a reversible neurological emergency caused by thiamine deficiency. Mortality is high without a timely diagnosis and thiamine replacement therapy. Chronic alcoholism is responsible for most cases. However, we report a rare case of WE induced by hyperemesis gravidarum with intrauterine fetal death. Diagnosis was established by classic clinical and magnetic resonance imaging (MRI) features and rapid response to intravenous thiamine. To the best of our knowledge, only a few cases with this condition have been reported in the literature.
A 32-year-old female patient presented with amenorrhea for 4 months, excessive vomiting for 3 months, and confusion and blurring of vision since the past few days. She also had difficulty in balancing herself. Her past medical history was not significant. The patient was given intravenous fluids and antiemetics in another hospital; however, her condition deteriorated. She was hemodynamically stable. Responses to verbal commands were occasionally irrelevant. She was oriented to place and person but not to time. Bilateral nystagmus was present. Truncal ataxia was present, even though limb coordination was intact. Tone, power, and reflexes were normal. Her laboratory investigations are presented in [Table 1].
Fluid-attenuated inversion recovery (FLAIR) sequences of magnetic resonance imaging (MRI) of the brain revealed bilateral symmetric hyperintensities in the mammillary bodies and medial thalamic nuclei adjacent to the third ventricle [Figure 1]a and [Figure 1]b. Diffusion-weighted imaging (DWI) showed hyperintensities in these areas, which appeared hypointense on the apparent diffusion coefficient map [Figure 1]c and [Figure 1]d, suggestive of restricted diffusion. Her ultrasonography of the abdomen revealed intrauterine fetal death; spontaneous expulsion of the intrauterine dead fetus occurred during the hospitalization course. The patient was immediately started on intravenous thiamine at a dose of 500 mg 3 times a day for 2 days, followed by 250 mg 3 times a day. Intravenous potassium replacement was also done. Her central nervous system (CNS) symptoms recovered completely over the next 4 days. She was discharged in a stable condition on oral thiamine, and was followed-up regularly.
WE is a metabolic disorder as a result of thiamine deficiency.
Thiamine is an important coenzyme in the Kreb's and pentose phosphate cycle. Thiamine deficiency leads to focal lactic acidosis, cerebral energy impairment, and depolarization of neurons, prompting cell necrosis and apoptosis. The body has approximately 18 days of thiamine storage. During pregnancy, there is an increased thiamine requirement, and there may be impaired absorption due to hyperemesis gravidarum. In addition, intravenous dextrose infusion, often given in hyperemesis, leads to further thiamine depletion.
The causes of WE are presented in [Table 2]. Hyperemesis gravidarum complicates 0.5–2.0% of the pregnancies and may lead to substantial nutritional deficiencies.
WE is primarily diagnosed clinically. Caine et al., proposed that WE is diagnosed if there exist any two of the following four signs: Nutritional deficiencies, oculomotor abnormalities, cerebellar dysfunction, and/or either an altered sensorium or memory impairment. Our patient clinically had all of these criteria: Prolonged vomiting, nystagmus, truncal ataxia, and was drowsy and confused. Di Gangi et al., in her review of literature reported that the ocular signs, especially nystagmus, were present in 95.2% of the patients. The other signs included cerebellar signs in 82.5%; ataxia in 74.6%, confusion in 60.3%, hypotonia in 60.3%, memory impairment in 52.3%, and severe alteration of consciousness in 30.1% of the cases. In a review of 49 cases of WE following hyperemesis gravidarum, the patient's mean (± standard deviation) age was 26.7 ± 4.9 years; WE manifested at a mean gestational age of 14.3 ± 3.4 weeks, and the mean duration of vomiting was 7.7 ± 2.8 weeks. The overall pregnancy loss rate attributable to WE was 47.9% (23 of 49). The clinical profile of our patient matches these reported figures.
Our patient showed elevated liver transaminase levels. Rotman et al., suggested that patients with hyperemesis and elevated liver enzymes are more likely to develop WE than those with normal values. Our patient also showed hypokalemia, which commonly accompanies hyperemesis. The laboratory assessment of blood transketolase activity and thiamine pyrophosphate are not very reliable. MRI is the imaging modality of choice in evaluating patients with possible WE because it is highly specific (93%). T1-weighted images may show hypointensity around the third ventricle and cerebral aqueduct. T2/FLAIR often shows bilateral symmetric hyperintensities in the mammillary bodies and medial thalami around the third ventricle, the tectal plate, and periaqueductal gray matter. DWI shows corresponding areas of restricted diffusion. WE responds to therapy when there is involvement of only the periaqueductal regions, medial thalami, and caudate nuclei; the involvement of the cortical regions suggests irreversible damage and a poor prognosis. Determining the extent of the injury helps in establishing the long-term maternal prognosis. Our case showed the classic MRI findings in the mammillary bodies and medial thalamus. Strong uniform enhancement, especially of the mammillary bodies, is seen in up to 80% of acute cases; however, it is much less common in non-alcoholic WE.
WE is treated by high doses of thiamine. Most authors recommend an intravenous dose, 500 mg per day given 4 times a day (q.i.d.) for 2 days. If an effective response is observed, 250 mg per day q.i.d. should be continued till the patient can tolerate oral thiamine. Then, oral thiamine should be continued, with a dose ranging from 60 to 100 mg daily for at least 3 months., Our patient responded dramatically to intravenous thiamine, and central nervous system manifestations recovered in 4 days. This further confirmed the clinical and imaging diagnosis of WE.
The mortality rate in WE ranges from 10 to 20%, however, many patients have persistent neurological deficits despite treatment. The manifestations start reversing in hours to days after thiamine administration; the oculomotor signs improve first followed by imbalance and altered sensorium., Regarding the fetal prognosis, WE is responsible for up to 50% of fetal deaths. Di Gangi et al., reported 34.5% spontaneous abortions, 9% elective abortions, and 3.6% fetal deaths in patients suffering from WE.
To the best of our knowledge, approximately 64 cases of hyperemesis gravidarum with WE have been described till date.,,,,, Our case is unusual as it had fetal death as well.
The possibility of WE should be considered in pregnant females with persistent vomiting, presenting with neurological manifestations, and the suspected cases should be supplemented with thiamine.
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[Table 1], [Table 2]