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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 11  |  Issue : 5  |  Page : 237-240

Wernicke's encephalopathy in a child with abdominal tuberculosis


1 Division of Child Neurology, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India
2 Department of Radiodiagnosis, Sir Ganga Ram Hospital, New Delhi, India
3 Department of Pediatric Endocrinology, Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India

Date of Submission06-Jun-2021
Date of Decision19-Aug-2021
Date of Acceptance20-Sep-2021
Date of Web Publication30-Oct-2021

Correspondence Address:
Dr. R K Sabharwal
Division of Child Neurology, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmrp.cmrp_57_21

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  Abstract 


Wernicke's encephalopathy (WE) is an acute neurological disorder, potentially fatal if untreated, caused by thiamine deficiency. A 15-year-old female patient with choledocholithiasis, cholecystitis and abdominal tuberculosis on antitubercular therapy presented with poor oral intake, bilious vomiting and encephalopathy. A prompt diagnosis of WE was made and confirmed by brain magnetic resonance imaging. The patient recovered completely after the administration of thiamine.

Keywords: Encephalopathy, thiamine, Wernicke


How to cite this article:
Sabharwal R K, Kumar P, Sud S, Kasawala KJ. Wernicke's encephalopathy in a child with abdominal tuberculosis. Curr Med Res Pract 2021;11:237-40

How to cite this URL:
Sabharwal R K, Kumar P, Sud S, Kasawala KJ. Wernicke's encephalopathy in a child with abdominal tuberculosis. Curr Med Res Pract [serial online] 2021 [cited 2021 Dec 3];11:237-40. Available from: http://www.cmrpjournal.org/text.asp?2021/11/5/237/329705




  Introduction Top


Wernicke's encephalopathy (WE) is an acute neuropsychiatric syndrome caused by thiamine deficiency that requires emergency treatment to prevent significant morbidity and mortality.[1] The disorder results from a deficiency in Vitamin B1 (thiamine), which in its biologically active form, thiamine pyrophosphate, is an essential coenzyme in several biochemical pathways in the brain. Thiamine acts as a cofactor for various enzymes in the carbohydrate metabolism, including transketolase, alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase and branched-chain ketoacid dehydrogenase complex. Thiamine deficiency causes neuronal injury in brain regions with high metabolic requirements. WE confirmed at autopsy had been missed by routine clinical examination in 75%–80% of cases. In children, about 58% of cases have been missed at routine clinical examination.[2] Encephalopathy, oculomotor dysfunction and gait ataxia is the classical triad of WE.[3] The presence of the classic triad appears to be more common in alcoholics and is seen in less than a third of non-alcoholics. In children, it is seen in patients with malabsorption, chemotherapy, anorexia nervosa, malignancies, total parenteral nutrition, etc. The diagnosis is clinical and supported by magnetic resonance imaging (MRI) changes and the dramatic response of neurological signs to parenteral thiamine.


  Case Report Top


A 15-year-old girl had undergone cholecystectomy with choledochoduodenostomy 6 months ago for choledocholithiasis and cholecystitis when she had presented with recurrent vomiting over 6 weeks. Her haemoglobin was 6.5 gm% and she received three packed red blood cell transfusions. Omental and lymph node biopsy revealed caseating necrosis of the nodes with epithelioid granulomas and Langhan's giant cells. Antitubercular therapy (ATT) with rifampicin, isoniazid (INH), pyrazinamide and ethambutol was started. A month later, she was admitted to our hospital with recurrent vomiting, loss of appetite and fever. She was dehydrated and jaundiced. Investigations revealed serum bilirubin of 2.8 mg%, more than five-fold rise of serum transaminases, and low serum albumin of 1.8 gm%. Computed tomography of the abdomen revealed multiple necrotic lymph nodes, haziness and stranding in the para-duodenal region, collapsed duodenum with thickened walls. The common bile duct and intra hepatic bile radicals were dilated. The possibility of ATT-induced hepatitis was considered and ATT was modified to ethambutol, streptomycin and levofloxacin. Parenteral albumin was administered, diet modified along with supportive care and proper nutrition. She was discharged 8 days later following clinical and liver function tests improvement.

She had been admitted now with intermittent bilious vomiting of 5 days' duration with decreased oral intake. INH had been reintroduced at another medical center a few days ago. On admission, she was thin, afebrile, mildly jaundiced and conscious. She had lost 9 kg of weight in the past 6 months and weighed 28 kg. She was confused, disoriented in time and place. She could recall only 1 object out of 4 after 1 min and high order single-digit and double-digit calculations were defective. Horizontal gaze in either direction evoked jerky nystagmus. She had upper limb dysmetria and heel to knee gross incoordination. On general examination, there was mild jaundice and mild dehydration. Pupillary reactions, fundus examination and bulbar reflexes were intact. Motor power was grossly normal, and reflexes were elicitable. Ankle jerks were sluggish. Her attention could not be sustained for a thorough sensory examination. No meningeal signs were elicited. Abdominal examination revealed no distension, but there was non-tender hepatomegaly of 3 cm.

The haemoglobin had fallen to 9.4 gm% with normal total counts and platelets. Serum bilirubin was 2.8 mg%. Serum transaminases were raised, serum glutamic-oxaloacetic transaminase 74 IU/L, serum glutamic-pyruvic transaminase 68 IU/L. The serum proteins, amylase, ammonia, thyroid functions, blood urea nitrogen, ceruloplasmin were in the normal range. Serum Vitamin B12 was 230 pg/ml (in the low normal range) for which she was administered parenteral vitamin B12, along with nutritional supplements. The electroencephalogram showed slowing of background rhythms, which was compatible with mild degree of diffuse brain dysfunction. Nerve conduction studies showed axonal neuropathy in the lower limbs. Cerebrospinal fluid examination was normal. Under the clinical impression of WE, intravenous thiamine was started (100 mg/day) and MRI brain with contrast was done, which showed increased signal in the head of caudate nuclei bilaterally, in the dorso-medial thalami, periaqueductal region, peri-3rd ventricular region and in mammillary bodies [Figure 1]a and [Figure 1]b bilaterally on T2W and fluid-attenuated inversion recovery images. These were characteristic findings of WE.[4] Patient's memory and calculations improved in 3–5 days. Nystagmus and ataxia improved and disappeared on 10 days of treatment.
Figure 1: (a) Magnetic resonance imaging brain with contrast shows increased signal in mamillary bodies. (b) Magnetic resonance imaging brain with contrast shows increased signal in the head of caudate nuclei bilaterally (small arrow) along the dorso-medial thalami(long arrow)

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However, the child had persistent vomiting and jaundice. On further evaluation, she was diagnosed to have choledochal cyst with choledocholithiasis with partial annular pancreas with focal segmental narrowing of duodenum along with extensive adhesions. Exploratory laparotomy with adhesiolysis with Roux-en-Y hepatico-jejunostomy with choledochal cyst excision with duodenoduodenostomy was done, following which the child improved and vomiting stopped. The patient was continued on replacement therapy of thiamine 100 mg daily orally and was discharged on oral thiamine supplement to be continued for at least 6 weeks.


  Discussion Top


WE was first described in 1881 by Carl Wernicke.[1] WE is caused by thiamine deficiency and is predominantly seen in alcoholics; however, it can also occur in a wide variety of other disorders. At the cellular level, the major enzymes involved are the α-ketoglutarate-dehydrogenase complex and the pyruvate-dehydrogenase complex in the tricarboxylic acid cycle, and transketolase in the pentose-phosphate pathway. Therefore, thiamine deficiency causes failure of metabolic demands and metabolic acidosis and cell death.[1],[5] Oxidative stress, inflammation and glutamate-mediated excitotoxicity are major contributors to neurodegeneration in WE. Furthermore, variation in the X-linked transketolase-like 1 gene might also contribute to genetic susceptibility to WE. Another gene coding for the high-affinity thiamine transporter protein SLC19A2 has been implicated in the pathophysiology of WE.[6]

Several cases of Wernicke encephalopathy in infants and young children have been reported secondary to inadequate dietary intake and thiamine deficiency. Magnesium deficiency acts as aggravating factor as it acts as a cofactor and is required in the proper catalytic action of transketolase. Further, its severe deficiency may lead to a refractory response to thiamine until magnesium is given. Malignancy is the most common underlying disorder in Western literature, precipitating WE in children.[2] Acute leukemias, non-Hodgkin's lymphoma, gastric carcinoma, allogenic bone-marrow transplants are amongst some of the causal malignancies in children. In children, WE may develop after gastrointestinal disorders and surgeries, particularly during the postoperative period as there is increased risk of thiamine deficiency due to various factors such as poor oral intake, vomiting, diarrhoea and malabsorption. WE has been reported in the pediatric population in association with liver disease, necrotising enterocolitis, food allergy, parenteral nutrition, short bowel syndrome, bowel obstruction and perforation, Crohn's disease, sepsis, pancreatitis and pyloric stenosis.[7]

The recommended dose of thiamine for an average, healthy adult is 1·4 mg/day or 0·5 mg of thiamine per 1000 kcal consumed. This dose is higher in children, in critically ill conditions, and during pregnancy and lactation. The World Health Organisation recommends daily oral doses of 10 mg thiamine for a week, followed by 3–5 mg/daily for at least 6 weeks, to treat mild thiamine deficiency. The recommended treatment for severe deficiency consists of 25–30 mg intravenously in infants and 50–100 mg in adults, then 10 mg daily administered intramuscularly for approximately 1 week, followed by 3–5 mg/day oral thiamine for at least 6 weeks.

Thiamine is absorbed in the duodenum and jejunum.[1] In our patient, the duodenum was diseased, the walls were thickened and it was collapsed. In an upper GI endoscopy, narrowing of the duodenum was observed with erosions in the duodenal bulb. An annular pancreas was causing duodenal compression. The child was unwell, with poor intake, weight loss, drug-induced hepatitis, multiple intra-abdominal pathologies. The stores of thiamine that can last up to 2 weeks must have been rapidly depleted in this ill child with an inadequate intake, especially when being managed with parenteral glucose mixed fluids, which accelerated the depletion of thiamine.

Our patient presented with nystagmus, ataxia and altered mental status. However, previous studies have detected the clinical triad in very few patients with WE.[1] The disorder presents with the loss of appetite, weakness, nausea, giddiness, memory loss, diplopia and difficulty in concentration early in the course, and later, the patient shows signs and symptoms of the classic triad, hallucinations and coma. Early intervention with thiamine replacement is required to reverse the symptoms of WE.[1],[8] It is common practice to initiate treatment with thiamine supplementation when Wernicke encephalopathy is suspected, without waiting for thiamine concentration results or even ordering such a test.[9] It is mandatory that thiamine is given before or concomitantly with intravenous administration of glucose when a diagnosis of WE is suspected because glucose alone can precipitate the disorder in thiamine-deficient individuals.

Initial improvements in acute symptoms can be observed within the 1st week, but it usually takes 1–3 months to resolve. Brain MRI is the most sensitive and important investigation in all suspected patients of WE. Medial thalami, mammillary bodies, periaqueductal region, tectal plate are typical sites of abnormal MRI signals as seen in our patient. Cerebellum, cranial nerve nuclei, red nuclei, dentate nuclei head, splenium, fornix and cerebral cortex are atypically involved, although they are more commonly affected in non-alcoholics. Testing blood thiamine levels lacks specificity and is not universally available. Measuring erythrocyte transketolase activity (baseline and after addition of thiamine pyrophosphate) and estimation of urinary excretion of thiamine are other tests; these are, however, not universally available, particularly in emergent situations.

Empiric thiamine replacement should be initiated as soon as WE is suspected. Delayed diagnosis and treatment may lead to irreversible neurological deficits, morbidity and death.[2] Treatment guidelines for WE in alcoholics are well defined.[1],[2],[5] However, there is no fixed guideline for pediatric patients.[2] Dosage of 50–100 mg daily has been suggested in paediatric patients with WE.[2],[10] Our patient was diagnosed early on clinical suspicion and treatment with thiamine led to a complete recovery. Thus, to avoid severe neurological deficits, it is imperative that high level of suspicion be maintained and early treatment initiated.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sechi G, Serra A. Wernicke's encephalopathy: New clinical settings and recent advances in diagnosis and management. Lancet Neurol 2007;6:442-55.  Back to cited text no. 1
    
2.
Vasconcelos MM, Silva KP, Vidal G, Silva AF, Domingues RC, Berditchevsky CR. Early diagnosis of pediatric Wernicke's encephalopathy. Pediatr Neurol 1999;20:289-94.  Back to cited text no. 2
    
3.
Lallas M, Desai J. Wernicke encephalopathy in children and adolescents. World J Pediatr 2014;10:293-8.  Back to cited text no. 3
    
4.
Zuccoli G, Siddiqui N, Bailey A, Bartoletti SC. Neuroimaging findings in pediatric Wernicke encephalopathy: A review. Neuroradiology 2010;52:523-9.  Back to cited text no. 4
    
5.
Hazell AS, Butterworth RF. Update of cell damage mechanisms in thiamine deficiency: Focus on oxidative stress, excitotoxicity and inflammation. Alcohol Alcohol 2009;44:141-7.  Back to cited text no. 5
    
6.
Guerrini I, Thomson AD, Cook CC, McQuillin A, Sharma V, Kopelman M, et al. Direct genomic PCR sequencing of the high affinity thiamine transporter (SLC19A2) gene identifies three genetic variants in Wernicke's Korsakoff Syndrome (WKS). Am J Med Genet B Neuropsychiatr Genet 2005;137B:17-9.  Back to cited text no. 6
    
7.
Basit S, Elsås T, Kvistad KA, Høsøien LS. Wernicke's encephalopathy because of pancreatitis in a young boy. Acta Ophthalmol 2011;89:e656-7.  Back to cited text no. 7
    
8.
Galvin R, Bråthen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA, et al. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol 2010;17:1408-18.  Back to cited text no. 8
    
9.
Berger MM, Shenkin A. Vitamins and trace elements: Practical aspects of supplementation. Nutrition 2006;22:952-5.  Back to cited text no. 9
    
10.
Manzanares W, Hardy G. Thiamine supplementation in the critically ill. Curr Opin Clin Nutr Metab Care 2011;14:610-7.  Back to cited text no. 10
    


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