Thiamine acts as a co-enzyme for decarboxylation and transketolase reactions. Blood pyruvate and lactate can increase in thiamine deprivation [1]. Wernicke encephalopathy is a neurological complication of thiamine deficiency characterized by nystagmus, ophthalmoplegia, ataxia, and confusion. It is mostly reported in chronic alcoholic adults and in few pediatric patients with other etiologies [2].

A 6-year-old girl was referred for encephalopathy, tachycardia and lactic acidosis. She was diagnosed with megacystis microcolon intestinal hypoperistalsis syndrome and had previously undergone several surgeries including total colectomy and subtotal ileum resection. She was admitted for six months with dehydration, electrolyte imbalance, poor oral intake and was receiving total parenteral nutrition (TPN) since then. She had developed encephalopathy and blurred vision three days back and, tachycardia and lactic acidosis several hours before admission to the intensive care unit.
On admission, the heart rate was 145/min, blood pressure was 100/65 mmHg with normal capillary refill time and no edema. She was lethargic, with Glasgow coma scale of ten. Neurological examination showed nystagmus and ankle clonus. Rest of the tendon reflexes and sensory system were normal.

Preliminary laboratory examination showed hemoglobin 9.7 g/dL, white cell count 10×10³ cells/µL, aspartate transaminase 108 U/L, alkaline phosphatase 352 U/L, serum procalcitonin 1.42 ng/mL, CRP 9.5 mg/L and lactic acidosis (pH 7.32, PCO₂ 26.6 mmHg, HCO₃ 15.9 mmol/L, lactate 7.3 mmol/L), Chest X-ray showed normal heart size and echocardiography was normal for systolic function (ejection fraction 65%). Her thyroid function test was normal.

Septic shock was diagnosed in the presence of fever, indwelling catheter for TPN and positive blood culture for gram-positive bacteria. Intravenous meropenem and teicoplanin were started empirically. Norepinephrine was added after fluid bolus but later discontinued as she progressively developed tachycardia and high blood pressure, and lactate increased to 13 mmol/L. It was noticed that she had not received water-soluble multivitamin infusion (MVI) due to a hospital-wide shortage for the last one month. Oral multivitamins were not substituted as physicians were unaware of the situation due to an electronic order system error. Thiamine 100 mg was administered intramuscularly. Lactate level decreased to 2 mmol/L within the first hour and tachycardia resolved within 12 hours. Magnetic resonance imaging (MRI) of brain showed diffusion restriction and signal increase on T2 weighted images in bilateral temporal, frontal and parietal cortex, corpus striatum, pons, and medulla oblongata. On the second day of thiamine treatment, her mental status improved, she became responsive to verbal stimuli and nystagmus disappeared. However, clonus persisted. Thiamine replacement (100 mg/day intramuscular) was continued for 14 days in addition to MVI in TPN.

Wernicke’s encephalopathy is an acute neurological disorder due to thiamine deficiency. The mental deterioration and cardiovascular instability in the index patient were due to thiamine deficiency as neurological symptoms started one month after MVI shortage and improved after initiation of thiamine replacement. She recovered with neurological sequela due to delayed replacement of thiamine.

The typical radiological finding of Wernicke encephalopathy is symmetric hyperintensities on T2 weighted MRI in the thalamus, mamillary bodies, periaqueductal gray matter, and tectal plate [3]. Atypical cases with cortical involvement are reported similar to index patient [4].

Thiamine deficiency may cause lactic acidosis which is rapidly reversible by vitamin replacement. Cases with profound lactic acidosis traced to thiamine deficiency were reported during a nationwide shortage of intravenous multivitamins in the United States in 1997 [5]. Erythrocyte transketolase activity and thiamine pyrophosphate effect tests were not available to us. However, the dramatic regression of neurological symptoms and lactic acidosis after thiamine replacement was suggestive of thiamine deficiency.

Clinical suspicion of thiamine deficiency might be life-saving, treatment should be started as early as possible before laboratory confirmation. In case of unexplained, refractory lactic acidosis, thiamine deficiency should always be considered in the differential diagnosis.

Contributors: TB: analyzed data and drafted the manuscript, reviewed literature; GE: helped in data analysis; TFK: analyzed data and reviewed the manuscript.

Funding: None; Competing interest: None stated.

References

1. World Health Organization, United Nations High Commissioner for Refugees. Thiamine deficiency and its prevention and control in major emergencies. 1999. Available at URL: https://www.who.int/nutrition/publications/emergencies/WHO_NHD_99.13/en/. Accessed on 12 Dec, 2019.

2. Shiozawa T, Shiota H, Shikata E, Kamei S, Mizutani T. Development of Wernicke’s encephalopathy during the period of oral food intake after subtotal colectomy for ulcerative colitis [translation]. Rinsho Shinkeigaku. 1995;35:169-74.

3. Zuccoli, G. and N. Pipitone, Neuroimaging findings in acute Wernicke’s encephalopathy: Review of the literature. AJR Am J Roentgenol. 2009; 192:501-8.

4. Zhong C, Jin L, Fei G. MR Imaging of nonalcoholic Wernicke encephalopathy: A follow-up study. AJNR Am J Neuroradiol. 2005; 26: 2301-5.

5. Centers for Disease Control and Prevention. Lactic acidosis traced to thiamine deficiency related to nationwide shortage of multivitamins for total parenteral nutrition—United States, 1997. MMWR. 1997; 46: 523-8.