Hyperemesis-Related Wernicke Encephalopathy

Wernicke encephalopathy (WE) is an acute neuropsychiatric emergency caused by thiamine (vitamin B1) deficiency. In pregnancy it is most often a complication of hyperemesis gravidarum. It is rare (about 1 in 100,000 pregnancies; under recognised) but potentially fatal.

Precipitants in hyperemesis:

• Prolonged vomiting (usually above 3 to 4 weeks, with weight loss above 5%) and poor oral intake.
• Carbohydrate loading. Dextrose containing fluids without thiamine precipitate WE by increasing thiamine demand for glucose metabolism.

Total body thiamine stores last only 18 to 20 days, and the requirement increases in pregnancy. Other precipitants: bariatric surgery, total parenteral nutrition without thiamine, alcohol use, and malabsorption.

Maternal mortality is up to 10 to 20%. Korsakoff syndrome (persistent amnestic disorder) occurs in about 80% of survivors with delayed treatment. Fetal loss is about 40 to 50%.

• Classic triad (present in only about 10 to 30%): ophthalmoplegia (nystagmus, lateral rectus palsy, conjugate gaze palsy), ataxia (wide based gait, truncal ataxia), and confusion (apathy, disorientation, impaired memory)
• Other features: visual blurring and diplopia, hypothermia, hypotension, tachycardia, coma, peripheral neuropathy, papilloedema and retinal haemorrhages, hearing loss, and lactic acidosis
• Onset after 4 to 6 weeks of vomiting, often in the second trimester
• High index of suspicion in any woman with hyperemesis and any neurological sign or confusion

• Clinical diagnosis; do not delay treatment for tests (diagnosis is made if there are two or more of dietary deficiency, oculomotor abnormalities, cerebellar dysfunction, or altered mental state or memory impairment)
• Blood tests: erythrocyte transketolase activity, whole blood thiamine pyrophosphate (low; sample before treatment), glucose, magnesium (replete, as magnesium is a cofactor), electrolytes, lactate, liver function, folate, B12, and ammonia
• MRI brain (T2 and FLAIR hyperintensity in medial thalami, mammillary bodies, periaqueductal grey matter, tectal plate, floor of fourth ventricle; mammillary body atrophy in chronic disease), sensitivity about 53%, specificity 93%
• Exclude differential diagnoses: eclampsia, posterior reversible encephalopathy syndrome, cerebral venous thrombosis, stroke, central pontine myelinolysis (rapid correction of hyponatraemia), infection

Treat immediately when suspected, with parenteral thiamine, before any glucose:

• Thiamine (as Pabrinex or equivalent) 500 mg IV three times daily for 2 to 3 days (infused over 30 minutes; pre-prepared high potency IV vitamin B and C preparations: two pairs of ampoules three times daily).
• Then thiamine 250 mg IV or IM daily for 3 to 5 days or until clinical improvement stops.
• Then oral thiamine 100 mg three times daily (or 100 mg daily) throughout pregnancy and until recovery of nutrition.
• Have resuscitation facilities available because anaphylaxis is rare.
• Correct hypomagnesaemia (magnesium sulfate 2 to 4 g IV), hypokalaemia and hypophosphataemia.
• Stop dextrose containing fluids until thiamine is given; use isotonic saline or Hartmann solution with thiamine.
• Treat hyperemesis with IV fluids and antiemetics (ondansetron 4 to 8 mg, metoclopramide 10 mg, cyclizine 50 mg, promethazine 12.5 to 25 mg, prochlorperazine).
• For refractory hyperemesis, give a short course of corticosteroids (hydrocortisone 100 mg IV twice daily then prednisolone 40 to 50 mg tapering) after 20 weeks or as per specialist advice.
• For refractory disease, give nutritional support (enteral or parenteral feeding with thiamine and trace elements).
• Prophylaxis: give thiamine 100 mg orally daily or 100 mg IV weekly (or 50 to 100 mg IV daily) to all women admitted with hyperemesis, particularly with vomiting for more than 3 weeks, before dextrose infusion.
• Maternal critical care for coma, and neurology and obstetric medicine input.
• Fetal considerations: consider termination only in severe cases with irreversible maternal neurological injury after multidisciplinary discussion; fetal growth surveillance.
• Follow up: neurology and neuropsychological assessment; recovery of ocular signs in hours to days, ataxia in weeks to months, and amnestic syndrome may persist.