Wernicke’s encephalopathy: An uncommon complication from hyperemesis gravidarum

Introduction

Nausea and vomiting are common in pregnancy, affecting 70–80% of all pregnant women. ¹ Hyperemesis gravidarum (HG) is distinguished from the benign nausea and vomiting of pregnancy by the presence of ketonuria and weight loss. ² Symptoms of HG peak around the ninth week of gestation and subside by the 20th week. ³ HG is associated with significant morbidity as 1–5% of patients with HG require hospitalization for severe dehydration and concomitant electrolyte imbalances. ³ Moreover, HG can potentially be associated with adverse pregnancy outcomes including low birth weight, miscarriage, and maternal morbidity such as micronutrient deficiency, and gastrointestinal bleeding_. ¹ One of the rare complications of HG is Wernicke’s encephalopathy, characterized by the triad of confusion, ophthalmoplegia, and ataxia. Without a high suspicion and rapid treatment for this condition, Wernicke’s encephalopathy can progress to Korsakoff syndrome, which is an irreversible condition consisting of confabulation as well as anterograde and retrograde amnesia. ⁴ Treatment for HG includes intravenous (IV) fluids and antiemetics, electrolyte replacement, and thiamine supplementation. ⁵ We present a case of HG complicated by thiamine deficiency and Wernicke’s encephalopathy.

Case

An 18-year-old primigravida presented to our hospital at 18 weeks' gestation with a five-day history of vertigo. She had a history of HG early in her pregnancy after a 30-pound weight loss, representing a loss of 18% of pre-pregnancy weight. After an initial regimen of oral antiemetics failed to control her symptoms, IV fluid replacement and IV ondansetron were initiated. On the day of the patient’s presentation to the Emergency Department, she reported an episode of near syncope and subsequent fall. The patient reported continued nausea and vomiting for the duration of her pregnancy despite home IV therapy and reported new-onset vertigo five days prior to admission. The patient’s partner reported gait abnormalities, strange affect, and periodic confusion since the onset of the vertigo. Upon review of systems, she denied headache, ear pain or fullness, hearing loss, tinnitus, diplopia, blurry vision, abdominal pain, diarrhea, melena, hematochezia, and hematemesis. She also denied recent illnesses and sick contacts. The patient had no other prior medical or surgical history, and denied tobacco, alcohol, and recreational drug use. On physical examination, she was tachycardic with a heart rate of 106 beats per minute and a blood pressure of 131/76 mmHg. Orthostatic vital signs were normal. The patient was awake, alert, and oriented to person, place, and time. Although she was noted to be slow to respond to questions, formal assessment of the confusion was not performed. Neurologic examination was significant for the presence of bilateral horizontal and vertical nystagmus. She had a positive Romberg maneuver, and due to the severity of symptoms and safety concerns, gait was not further assessed. The remainder of the physical examination was within normal limits apart from dry mucous membranes. Laboratory testing was ordered and revealed profound hypokalemia with a potassium level of 2.5 mmol/L and a urinalysis demonstrating 2+ ketones. A complete blood count and electrolytes were within normal limits. The patient was admitted to the hospital for further workup of her ongoing vertigo. After initial assessment, she was diagnosed with dehydration secondary to HG and was administered 3.5 L of 5% dextrose in lactated Ringers intravenously as well as IV promethazine. Electrolyte repletion was also initiated. Magnetic resonance imaging (MRI) of the brain was ordered to rule out a central cause of the patient’s vertigo. Although increased signal in the medial thalamus was initially thought to be a potential artifact, a secondary review by the radiology team revealed that the findings were consistent with Wernicke’s encephalopathy, as demonstrated by an area of restricted diffusion in the medial thalamic nuclei (see Figure 1).

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Figure 1.

Magnetic resonance imaging of the brain revealing restricted diffusion in the medial thalamic nuclei, as seen in Wernicke’s encephalopathy.

This abnormality, paired with the patient’s history of malnutrition secondary to HG, supported a diagnosis of Wernicke’s encephalopathy. The patient was administered IV thiamine 200 mg every 8 hours for a total of 48 hours and was subsequently changed to oral thiamine 100 mg daily. Unfortunately, on the second day of admission, the patient suffered an intrauterine fetal death. The symptoms of vertigo, altered mental status, nausea, and vomiting resolved, and the patient’s nystagmus significantly improved. The patient was discharged on hospital day 5 with out-patient follow-up.

Discussion

HG affects 0.3–2.3% of all pregnancies; it is defined as persistent vomiting with an associated weight loss exceeding 5% of pre-pregnancy weight, in addition to ketonuria unexplained by other causes. ² Common maternal complications of HG are dehydration and nutrient deficiencies, as well as and complications arising from intractable vomiting such as a Mallory--Weiss tear, gastrointestinal bleeding, and pneumomediastinum. Fetal complications of the disease include miscarriage, low birth weight, and preterm delivery. ⁶ The association of HG with placental dysfunction and perinatal death, however, remains controversial.^7,8 Although volume repletion and symptomatic therapy for nausea are the mainstay of therapy for HG, the Royal College of Obstetricians and Gynecologists currently recommends systematic supplementation with thiamine for all women with prolonged vomiting. The administration of thiamine should be prior to receiving a dextrose infusion to prevent the development of Wernicke’s encephalopathy. ⁵ Thiamine, a cofactor for many enzymatic reactions, plays an integral role in cerebral energy utilization. Its deficiency can lead to neuronal damage through metabolism inhibition in regions of the brain where metabolic requirements are high. Events such as blood-brain barrier breakdown, N-methyl-D-aspartic acid receptor-mediated excitotoxicity, and increased reactive oxygen species have been implicated in thiamine deficiency-induced neurotoxicity. ⁹ Although alcoholism is the most common cause of Wernicke’s encephalopathy, this disorder also occurs in the setting of poor nutrition caused by malabsorption, poor dietary intake, and rarely as a complication of HG.^2,9 Wernicke’s encephalopathy presents with a triad of gait ataxia, ophthalmoplegia, and confusion; the presence of all three findings, however, is uncommon.^10,11 In a case series of patients with Wernicke’s encephalopathy in the setting of pregnancy, while ocular manifestations were present in 96% of patients, only 47% of patients had all the findings included in the classic triad. ¹¹ In addition to careful clinical assessment, neuroimaging can further support the diagnosis. Bilateral and symmetrical hyperintensities on T2-weighted and FLAIR MRI images can be noted in the thalami, mamillary bodies, tectal plate, and periaqueductal area of patients with Wernicke’s encephalopathy. ¹² As in this case, radiographic findings can support the diagnosis. However, Wernicke’s encephalopathy is mainly identified on clinical presentation alone. Thus, whenever suspected in the right clinical context, even in the absence of radiologic confirmation, Wernicke’s encephalopathy should be considered a medical emergency and immediate thiamine repletion should be given. If left untreated, Wernicke’s encephalopathy could potentially progress to Korsakoff syndrome, a late neuropsychiatric irreversible disease characterized by anterograde and retrograde amnesia as well as confabulation.^5,11 Importantly, the development of Wernicke’s encephalopathy during pregnancy has also been associated with a fetal mortality rate as high as 48%, and close fetal monitoring is thus warranted. ¹¹

Several lessons can be learned from our case. Firstly, the presence of protracted vomiting should have prompted administration of thiamine supplementation, particularly prior to initiating dextrose-containing fluid repletion. Indeed, early administration of IV thiamine may have prevented the development of Wernicke’s encephalopathy. Secondly, the administration of thiamine was delayed by 24 h and was given only after radiographic evidence of Wernicke’s encephalopathy was confirmed. Clinicians should therefore maintain a high suspicion for Wernicke’s encephalopathy in the setting of HG to recognize typical signs and symptoms, although they may not all be present at once, and initiate urgent treatment. Finally, despite adequate therapy following diagnosis, fetal death ensued. Patients should therefore be closely monitored and adequately counseled on the increased fetal mortality associated with this condition.

In conclusion, vertigo during pregnancy should be carefully evaluated and physicians should maintain a broad differential diagnosis, including Wernicke’s encephalopathy. Although Wernicke’s encephalopathy is uncommonly seen in HG, the diagnosis can be easily missed in the young healthy woman. Not all three symptoms in the classic triad need to be present to diagnose Wernicke’s encephalopathy. Therefore, the presence of one or two symptoms and a suspected diagnosis should lead to immediate treatment. An MRI of the brain can rule out other central causes of vertigo, or as in our case, help to establish this rare diagnosis. Intravenous thiamine supplementation is recommended for all women with protracted vomiting. When treating HG, clinicians should have a high level of suspicion for Wernicke’s encephalopathy if neurologic complaints occur, as failure to provide timely treatment could lead to fatal maternal and fetal consequences.