Wernicke-Korsakoff Syndrome from Hyperemesis Gravidarum

To editor: Wernicke encephalopathy (WE) is an acute neurological disorder caused by a deficiency of vitamin B1 (thiamine), with a prevalence of 1.3% in autopsy studies.1 Eighty-four percent of patients with WE will develop Korsakoff syndrome, which is characterized by amnesia and confusion.2 Although WE is more common in alcoholics, it can also be caused by vomiting, malnourishment, and other situations. Hyperemesis gravidarum, a severe form of vomiting in pregnancy affecting 0.3% to 3% of pregnancies, can also cause thiamine deficiency.3 Although there are no specific diagnostic criteria for hyperemesis gravidarum, it is generally defined as persistent vomiting in pregnancy that has no other identifiable cause. Risk factors of hyperemesis gravidarum include a family history of hyperemesis, multiple gestation, and history of hyperemesis gravidarum. Hyperemesis gravidarum can be associated with other complications such as nutritional deficiencies, esophageal injury, psychosocial effects, and poor fetal outcomes.3 We report a case of WE associated with hyperemesis gravidarum. This case suggests that providers should have a high degree of suspicion for WE and initiate early treatment in pregnant women with severe vomiting and neurologic symptoms.4 The patient provided informed consent for publication of this case. Case presentation A 16-year-old (gravida 1, para 0) patient was transferred to our institution from a local emergency department for inpatient care at 15+4 weeks of gestation secondary to hyperemesis, altered mental status, slurred speech, difficulty ambulating, visual changes, and difficulty hearing. Her mother reported nausea and vomiting for the past 2 months with emesis occurring 4 times a day. The family also reported other symptoms such as progressive weakness, amnesia, and excessive somnolence. She had a history of generalized anxiety disorder, major depressive disorder, and one prior episode of intentional overdose of acetaminophen before pregnancy. It is possible that her symptoms were not recognized earlier due to this history as the mother stated that the patient liked to be alone. She denied tobacco, alcohol, or drug use and did not have any other known risk factors for hyperemesis gravidarum. Initial examination at the outside emergency department showed that the patient had notable ataxia and was not oriented to time or location. However, she was able to follow simple commands and answer straightforward questions. At this time, differential diagnoses for her included metabolic encephalopathy, drug abuse, alcohol intoxication, intracranial hemorrhage, cerebrovascular accident, cavernous sinus thrombosis, hyperemesis gravidarum, viral syndrome, and seizures. Laboratory results, including complete blood count, alcohol level, urine drug screen and urinalysis, were all negative. A complete metabolic panel showed hypokalemia to 2.7 mEq/L. A computed tomography of the head with contrast was initially obtained to rule out acute intracranial abnormalities and was unremarkable. OB/GYN consultation was obtained and transfer with inpatient admission was recommended. After the transfer was accepted, she was given an initial dose of thiamine 100 mg intravenously (IV) and ondansetron while en route to our hospital. Because of the patient’s clinical picture, neurology consultation was obtained, and a magnetic resonance imaging (MRI) was performed. Routine multiplanar, multisequence, T2-weighted, diffusion-weighted, fluid-attenuated inversion recovery MRI of the brain showed symmetrical, abnormal restriction in the pulvinar and dorsomedial thalamic nuclei known as the “double hockey-stick sign” and the hyperintensity in the thalami, midbrain, and peri-aqueduct area, which are findings known to be associated with WE (Figure 1A and B).5Figure 1: Findings of brain magnetic resonance imaging with T2-weighted fluid-attenuated inversion recovery sequence. A On readmission with hyperemesis (white indicate double hockey-stick sign and the hyperintensity). B At 2 months after treatment with thiamine.The patient was started on thiamine 500 mg IV twice a day for 3 days followed by 250 mg IV for 5 days in addition to a multivitamin injection, folic acid, and vitamin B6. She was also started on famotidine in addition to scheduled ondansetron and doxylamine succinate/pyridoxine three times daily. Throughout her 10-day hospital stay, her condition significantly improved, and she had full resolution of her nausea, emesis, and abdominal pain. With resolution of the acute symptoms of WE, she was discharged to home with close follow-up. She was prescribed thiamine 100 mg daily and continued on doxylamine with pyridoxine, ondansetron, famotidine, and various prenatal supplements. At neurology follow-up 2 months after discharge, the patient complained of blurry vision in her left eye. On examination, left eye esotropia and ophthalmoplegia were noted, although it had improved from her previous examination. She also continued to have some difficulty in tandem gait. No other neurological deficits were seen at this time. A repeat MRI of the brain showed resolution of the previous abnormalities on the prior MRI study (Figure 1C). Approximately 4 months after discharge, the patient was admitted for induction of labor, and she had an uncomplicated spontaneous vaginal delivery at 39 weeks of gestation. The baby had Apgar scores of 7/8 and a birth weight of 2920 g. She had minimal blood loss and recovered well after delivery. She was discharged to home in stable condition. After delivery, the patient continued to follow up with neurology regularly and had slow improvement of her left eye abnormalities and gait with continued thiamine supplementation. Follow-up 14 months after discharge showed improvement of her tandem gait and full resolution of her left eye esotropia and ophthalmoplegia. Because of normal thiamine level and improvement in her symptoms, supplementation was discontinued. She continues to follow up with neurology and ophthalmology on a regular basis to monitor gait, thiamine levels, and vision. Discussion WE has many potential risk factors such as alcohol abuse, repeated vomiting, malignancy, gastrointestinal issues, and malnutrition—all of which cause thiamine deficiency.1 While hyperemesis gravidarum can also result in acute thiamine deficiency, it is not often associated with WE. WE presents with a triad of symptoms including ocular signs, ataxia, and confusion, and its presence during pregnancy may put patients at risk for permanent neurological dysfunction, Korsakoff syndrome, miscarriage, preterm birth, intrauterine growth restriction, and death.2,5,6 Although 70% to 90% of pregnant women experience nausea and vomiting, few develop hyperemesis gravidarum. Women who are experiencing prolonged or excessive vomiting should receive thiamine supplementation (usual dosing is 100 mg intramuscular (IM) or IV) to reduce the potential development of WE; however, higher doses are warranted when WE is diagnosed.4 Recommended dosing for thiamine supplementation in WE is 500 mg IV three times daily for 2 days, followed by 250 mg IV or IM once daily for an additional 5 days.7 It is important to emphasize the correct dosing for thiamine as inadequate thiamine dosing was reported in 63% of cases in the largest systematic review (177 cases). Age may also impact the severity of WE symptoms, with younger patients potentially having better outcomes, although more evidence is needed to say this with certainty.8 In our literature review, we were not able to identify a patient as young as ours. Providers must maintain a high index of suspicion for WE and monitor for ocular signs, ataxia, and confusion. Aggressive treatment with adequate thiamine dosing is critical to avoid potentially life-threatening complications for both the mother and fetus.