Background

The term gestational trophoblastic disease encompasses premalignant and malignant conditions arising from trophoblastic cells. Premalignant disorders include complete or partial hydatidiform mole, whereas malignant disorders include invasive mole, choriocarcinoma and placental-site trophoblastic tumour.1 A complete hydatidiform mole typically results from fertilisation of an empty ovum by a single sperm that duplicates its DNA, resulting in a 46 XX karyotype. About 10% of complete moles occur when an ovum lacking chromosomes is fertilised by two sperm, resulting in a 46XY karyotype of paternal origin. Conversely, partial hydatidiform moles are triploid in nature and occur when two sperm fertilise a single ovum.1 2

Pre-eclampsia, a hypertensive disorder of pregnancy complicating 2%–8% of pregnancies, is a syndrome which presents as new-onset hypertension after 20 weeks’ gestation accompanied by proteinuria and/or evidence of maternal acute kidney injury, liver dysfunction, neurological features, haemolysis or thrombocytopenia or fetal growth restriction.3 The occurrence of haemolysis, elevated liver enzymes and low platelet count, referred to as HELLP syndrome, is considered a severe form of pre-eclampsia.4 A related severe manifestation is posterior reversible encephalopathy syndrome (PRES)—a clinico-radiological syndrome characterised by symptoms including headache, seizures, altered consciousness and visual disturbances. PRES is commonly, but not always, associated with acute hypertension.5 The symptoms of PRES vary widely with various neurologic symptoms as well as gastrointestinal symptoms such as nausea and vomiting.6 Although pre-eclampsia and HELLP syndrome rarely occur before 20 weeks of gestation, reports have suggested early occurrences of these hypertensive disorders specifically in the setting of a molar pregnancy.7–11

Case presentation

The patient is a gravida 1 para 0 female in her mid 20s at 16 weeks 5 days dated by 6 week ultrasound who presented to an outside emergency department with a 3 day history of progressive generalised abdominal worse in the epigastric region which ‘felt like someone punched me’ which radiated to her back, arms and shoulders. She has no significant risk factors for pre-eclampsia other than nulliparity. At the outside facility, the patient had multiple systolic blood pressures greater than 160 mm Hg and had a witnessed 30 s seizure which resolved with an intravenous (IV) injection of 2 mg of lorazepam and 4 g magnesium sulfate loading dose. She received a CT scan of her head which was negative for signs of mass effect or gross haemorrhage or ischaemia. She then received two doses of IV labetalol and was initiated on a magnesium sulfate infusion for seizure prophylaxis pending transfer to our institution. At the outside hospital, the patient’s laboratory work up was significant for dipstick urine protein 3+, aspartate aminotransferase (AST) 100 U/L, alanine transaminase (ALT) 57 U/L, platelet count was 169 000/uL, haemoglobin was 12.2 g/dL and her lactate dehydrogenase (LDH) was 387 U/L. On admission, the patient met criteria for eclampsia and her laboratory work up showed a trend towards HELLP (platelets 79 000/uL, AST 144 U/L, ALT 96 U/L, LDH 482 U/L, haemoglobin 8.7 g/dL). Haemolysis was defined by the decreasing haemoglobin and elevating lacate dehydrogenase. The beta human chorionic gonadotropin (HCG) level was greater than 200 000 mIU/mL. Of note, the thyroid stimulating hormone was low at <0.020 uIU/mL with a normal T4 of 1.44 ng/dL. Bedside ultrasound suggested the presence of an enlarged cystic placenta and a growth restricted fetus (estimated fetal weight 124 g, second percentile Hadlock) with heart tones in the 130 s and a biparietal diameter and head circumference less than the first percentile Hadlock. The patient and her family were counselled and the decision was made to proceed with misoprostol induction and termination of the pregnancy. After initiation of the induction, the patient developed significant vaginal bleeding and was taken to the operating room for an uncomplicated dilation and evacuation. After the procedure, the patient developed progressive visual blurring and 4+ hyperreflexia. MRI of the brain with and without contrast was obtained with findings significant for PRES. Specifically, the MRI revealed T2 high-signal lesions within the cortex of the bilateral occipital lobes (figure 1), scattered lesions within the bilateral cerebellar hemispheres, left meningeal enhancement and gyral swelling in the right parietal lobe.

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Figure 1

MRI image demonstrating T2 high-signal lesions within the cortex of the bilateral occipital lobe (figure developed by author and retrieved from patient chart).

Neurology was consulted and recommended blood pressure control with extended-release nifedipine and initiation of levetiracetam for seizure prophylaxis. The patient did complete the 24-hour magnesium sulfate infusion for eclampsia prophylaxis. Patient’s visual symptoms stabilised and resolved, and the hyperreflexia abated. Her liver function tests, platelets and LDH also returned to normal soon thereafter. The 48-hour postprocedure beta-hCG was 79 033 mIU/mL, trending down from >200 000 mIU/mL noted prior to the procedure. The patient received contraceptive counselling to prevent pregnancy during postevacuation gestational neoplastic disease surveillance period. She was initiated on oral hormonal contraceptives.

Differential diagnosis

After the patient was transferred, epilepsy was considered briefly but ruled out due to no history of prior seizures and the seizure occurring in a setting of newly elevated blood pressure. Gestational hypertensive disease does not typically occur so early in pregnancy, but this patient had evidence of molar pregnancy (abnormal findings on ultrasound and abnormally elevated beta-HCG) which would explain the early onset. Cerebrovascular accident was on the differential but did not appear on imaging and the neurologic symptoms improved with antiepileptic medications, magnesium sulfate and blood pressure control which is more consistent with eclampsia and PRES.

Treatment

Ultimately, the source of her gestational hypertensive disease was the partial molar pregnancy which was treated with dilation and evacuation. She required stabilisation several times for the various manifestations of her pre-eclamptic disease. She was treated with IV labetalol and magnesium sulfate for maternal stabilisation during her eclamptic seizure. For stabilisation of neurologic symptoms of PRES, she was initiated on levetiracetam for seizure prophylaxis and extended-release nifedipine for blood pressure control. See figure 2 for a summary.

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Figure 2

Treatment and stabilisation of severe pre-eclamptic disease (figure developed by author). ED, emergency department; HELLP, haemolysis, elevated liver enzymes and low platelets syndrome; PRES, posterior reversible encephalopathy syndrome.

Outcome and follow-up

The histologic pathology demonstrated the presence of chorionic villi composed of both large hydropic and smaller normal-appearing villi. The gross pathologic examination revealed a 69.3 g female fetus compatible with gestational age of approximately 14–15 weeks with caudal neurocutaneous defect with abnormal localisation of brain tissue, and overall unremarkable fetal membranes. The genetic profile of the villous tissue consisted of two sets of dispermic paternal alleles in addition to one set of maternal alleles consistent with a partial mole diagnosis. Per National Comprehensive Cancer Network (NCCN) guidelines, the patient was advised to undergo weekly beta-hCG until negative, followed by 3 weekly consecutive negative levels before spacing measurements to every 3 months for a period of 6 months. Because the patient was very complaint with follow-up, she underwent modified testing of every 2 weeks until non-pregnancy levels were achieved and then monthly for 6 months (figure 3). She became pregnant at her sixth month of non-pregnancy level surveillance and successfully delivered at term.

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Figure 3

Beta-HCG surveillance (figure developed by author). HCG, human chorionic gonadotropin.