Wernicke’s Encephalopathy (WE) Associated with Hyperemesis Gravidarum (HG) Presenting with Psychiatric Morbidity: Description of Two Cases

Abstract

Background:

Hyperemesis gravidarum (HG) refers to intractable vomiting during pregnancy and is rarely associated with Wernicke’s encephalopathy (WE). HG-associated WE can lead to mortality and permanent cognitive impairment if left untreated. In this report, we present two cases of WE following HG occurring in the context of comorbid severe depression.

Case Description:

In the first case, a 29-year-old female developed HG and WE during the second month of pregnancy, followed by an episode of severe depression with catatonia. In the second case, a 23-year-old female with bipolar disorder presented with HG for two months during pregnancy, followed by an episode of severe depression and a fractured mandible due to a fall.

Conclusion:

Thiamine should be considered in women experiencing prolonged vomiting during pregnancy, and they should be closely monitored for features of WE.

Wernicke’s encephalopathy (WE), emerging due to a deficiency of thiamine (Vitamin B1), is a neuropsychiatric condition that presents with the triad of ataxia, ophthalmoplegia, and mental status change due to prolonged vitamin B1 deficiency. ¹ Although rare, it can lead to mortality and permanent cognitive impairment if left untreated. WE is commonly reported in the context of alcohol withdrawal. However, this can also occur in patients experiencing prolonged vomiting, eating disorders, those with dietary deficiencies, and those receiving various chemotherapeutic agents. ¹

Hyperemesis gravidarum (HG) refers to intractable vomiting during pregnancy and is seen in up to 3% of pregnancies. ² HG during pregnancy is associated with malnutrition, vitamin deficiencies, and severe complications like WE.^1,2 However, the exact prevalence of WE in the context of HG is not known, and there is limited literature on the same. A few cases of depression predisposing to WE have been reported in patients with cancer. ³ There are also case reports of WE due to HG masquerading as a depressive disorder. ⁴ This report presents two cases of WE following HG occurring in the context of comorbid severe depression.

Case 1

A 29-year-old female who feared consuming medications since childhood and had no other significant personal, past, or family history developed acute onset episodes of vomiting during the second month of her first pregnancy. Initially, she would have three to five episodes of vomiting after eating food or drinking water. So, she started avoiding food and water intake. Over a month, the frequency of vomiting increased to 8 to 10 times per day, along with excessive salivation. About six weeks after the onset of vomiting, she also developed persistent low mood, loss of interest, easy fatigability, reduced interaction, crying spells, excess sleepiness, decreased appetite, and poor self-care, leading to marked psychosocial dysfunction, and she stopped working due to the same. Later, the depressive symptoms progressed, and she developed features of starting, mutism and negativism. She was admitted to a local hospital and received intravenous fluids for a week. The depressive symptoms, catatonic symptoms, and intractable vomiting continued as such, and after discharge from the hospital, she was found to have difficulty in walking. She was later taken to a neurologist and, on examination, was found to have inward rolling of the left eye along with horizontal gaze nystagmus, dysdiadokokinesia, inability to perform finger nose test, and ataxia. Magnetic Resonance Imaging (MRI) of the brain showed signal alteration in bilateral thalami, periaqueductal region, and mammillary bodies. HG and WE were diagnosed, and she was managed with intravenous thiamine supplementation of 500 mg thrice daily. She was referred to our center at 18 weeks gestation and advised of Medical Termination of Pregnancy (MTP). Initially, she was admitted to the gastroenterology unit because of her poor oral intake. A psychiatry consultation was sought, and a diagnosis of catatonia secondary to depressive disorder (severe depressive episode with catatonia vs. organic mood disorder) was considered, based on the International Classification of Diseases, tenth revision (ICD-10) criteria.

The thyroid profile of the patient was normal, and there were no signs and symptoms of raised blood pressure. Her Bush Francis Catatonia Rating Scale (BFCRS) score was 10 at the baseline assessment, which decreased to three after the lorazepam challenge test. She was continued on thiamine supplementation and started on syrup fluoxetine 10 mg/day and lorazepam 4 mg/day. MTP was done in the same week, as the patient was not in a state to care for herself and her pregnancy. After a week, when an attempt was made to taper off lorazepam, her BFCRS score increased to 16. Consequently, electroconvulsive therapy (ECT) was started after consultation with neurologist, anesthetist, gynecologist, and gastroenterologist. Six effective ECTs were delivered, with which BFCRS decreased to o, and her depressive symptoms also resolved.

Meanwhile, fluoxetine was increased to 30 mg/day. Her cognitive functions were monitored, but there was no further worsening of cognitive functions during ECT. After her depression resolved, she continued to have persistent cognitive deficits and ataxia. These symptoms showed minor improvement over a follow-up period of four years, and she continued to remain dysfunctional due to the same.

Case 2

A 23-year-old female, married, belonging to an extended family of middle socioeconomic status and rural background, with no significant past or family history, diagnosed with bipolar disorder since the age of 20 years, presented with severe depression to the emergency. Exploration of the history revealed that she was pregnant for four months, had had HG for two months, and had a history of falls since the third month of gestation, with one such episode leading to severe injury to her jaw. On examination, she was found to have pallor, a squint in the left eye, nystagmus, and a lurching gait. Her baseline MMSE score was 22. A diagnosis of bipolar affective disorder, a current episode of severe depression without psychotic symptoms as per the ICD-10, was considered. Additional diagnoses included pregnancy (16 weeks gestation), anemia, mandible fracture, HG, and WE. The thyroid profile did not reveal any abnormality. Neurology consultation was sought, and she was started on intravenous thiamine supplementation of 500 mg thrice daily for the initial week, followed by 300 mg/day for the next three weeks, and then 100 mg thrice daily. After an obstetrics consultation, MTP was done as she could not care for herself and the pregnancy. Dental consultation for the fractured mandible was sought, and conservative management was advised. After pre-lithium investigations, lithium was started, and the dose was increased to 450 mg/day with monitoring of serum lithium levels. She was also started on Tab. escitalopram, and the dose was increased to 15 mg/day along with Tab. Quetiapine 150 mg/day. With these medications, her Beck Depression Inventory score decreased from 24 to 6, and her cognitive functions improved. Over the next 2.5-year follow-up period, she maintained well, with no relapse of affective symptoms and adequate cognitive functioning.

Discussion

Both of our cases highlight the occurrence of WE during the first trimester of pregnancy in women experiencing HG. In one case, HG and manifestations of WE preceded the onset of psychiatric manifestations. In contrast, the second case was already diagnosed with bipolar disorder prior to presentation with WE. In the first case, the occurrence of depression and catatonia can be attributed to WE and depression may be an epiphenomenon.

WE is a rare complication of HG-associated during pregnancy. A 2006 review identified 48 published cases, and a second systematic review published in 2019 included data from 146 case reports/series containing information about 177 cases.^2,5 These reviews suggest that the mean age of patients with HG exhibiting manifestations of WE is about 27 years, and the median duration of excessive vomiting is about seven weeks (range: 1–30 weeks) before WE symptomatology emerges and the mean duration of pregnancy before the onset of features of WE is about 15 weeks. Regarding typical symptoms of WE, available data suggest that nystagmus is seen in 76.8% of the cases, and ophthalmoplegia is seen in 34.5% of patients. Ataxia is noted in 83.1% of the reported cases, and cognitive problems are noted in 83.6%. ² Among the reported cases in which MRI was done, changes were seen in the thalamus and adjoining area, consistent with WE in 91% of cases. ² Both of our cases had the classical triad of WE; one was 23 years old, and the other was 29 years old. In terms of duration of pregnancy too, both of our patients presented during the fourth month of pregnancy, which is consistent with the existing literature. An MRI was done on one of our patients, and the findings were consistent with WE.

Both the reviews suggest that in half of the WE patients, the fetus was lost either due to spontaneous miscarriage or abortion.^2,5 In both cases, we had to go for MTP after discussing it with the patient and the spouse. However, the maternal outcomes were good.

Korsakoff syndrome, or Wernicke-Korsakoff syndrome, can emerge due to WE, a chronic condition characterized by marked chronic memory loss. ⁶ In the long run, one of our patients exhibited features of Korsakoff syndrome.

The Royal College of Obstetricians & Gynaecologists ⁷ recommends 100 mg intravenous or intramuscular thiamine as prophylaxis for HG patients to prevent the development of WE. Once WE evolve, the Royal College of Physicians ⁸ recommends 500 mg of parenteral thiamine given three times daily until acute symptoms of WE resolve. This is essential to prevent complications such as mortality and severe cognitive deficits. Administration of dextrose-containing intravenous fluids prior to administration of thiamine can precipitate WE and should be avoided before thiamine supplementation. ⁹ In our first case, the patient received intravenous fluids before presentation at our center, which could have worsened the symptoms of WE.

Previous case reports have not reported much about the presence of psychiatric morbidity among patients with WE associated with HG. A review of the literature suggested that WE is very infrequently diagnosed in psychiatric patients. ¹⁰ This could be due to the non-involvement of mental health professionals in assessing such patients. In one of our cases, the patient was diagnosed with depression by the psychiatry team, and the other case was diagnosed with bipolar disorder prior to the pregnancy. Our findings suggest that besides consulting neurologists, obstetricians should consult psychiatrists, too, when a pregnant female is considered to have WE, as it may be related to poor nutritional status due to underlying mental disorders or the occurrence of mental disorders as was seen in our patients.

To conclude, our cases and the existing literature highlight the fact that thiamine supplementation should be considered in pregnant women experiencing prolonged vomiting during pregnancy. Moreover, in women exhibiting signs and symptoms suggestive of thiamine deficiency, thiamine should be supplemented as quickly as possible. Further, for women presenting with psychiatric manifestations for the first time or experiencing a relapse during the pregnancy, a history of HG should be evaluated carefully, and appropriate treatment should be instituted.