Home About us Current issue Ahead of Print Back issues Submission Instructions Advertise Contact Login   

Search Article 
Advanced search 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 754 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 

Table of Contents   
Year : 2021  |  Volume : 32  |  Issue : 5  |  Page : 1456-1460
Wernicke's encephalopathy – An oddball complication of nephrotic syndrome

1 Department of Pediatrics, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
2 Department of Diagnostic and Interventional Radiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

Click here for correspondence address and email

Date of Web Publication4-May-2022


Metabolic encephalopathies are a common cause of altered mental status in various states of malnutrition. However, a high index of suspicion is required to recognize them and differentiate Metabolic Disorders from other causes of altered mental status such as infections. A 6-year old with steroid-resistant nephrotic syndrome (NS), peritonitis, and prolonged diarrhea and vomiting, developed a brief episode of altered mental status six days after starting tacrolimus. On imaging, there were features suggestive of Wernicke’s encephalopathy and it ruled out other causes of seizure in the given scenario. The child was treated with thiamine supplementation and the changes reversed four weeks after treatment. This is to emphasize that although an uncommonly reported complication of nephrotic state, one should have a high index of suspicion for these metabolic encephalopathies, especially in the setting of malnutrition, where these children are highly predisposed to multivitamin deficiency.

How to cite this article:
Mittal A, Tiwari S, Sureka B, Singh K. Wernicke's encephalopathy – An oddball complication of nephrotic syndrome. Saudi J Kidney Dis Transpl 2021;32:1456-60

How to cite this URL:
Mittal A, Tiwari S, Sureka B, Singh K. Wernicke's encephalopathy – An oddball complication of nephrotic syndrome. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 May 25];32:1456-60. Available from: https://www.sjkdt.org/text.asp?2021/32/5/1456/344767

   Introduction Top

Neurological complications are known in nephrotic syndrome (NS). Some of the common causes of a single neurological event in NS are intracranial vascular thrombosis, posterior reversible encephalopathy syndrome (PRES), toxicity related to use of calcineurin inhibitors, intracranial infections i.e. meningitis and metabolic causes such as hypocalcemia and hypomagnesemia which may be precipitated during a relapse. Here we discuss the uncommonly seen metabolic encephalopathy in a child with relapse of NS which highlights the consequences of malnutrition in these children and barely reported in children with NS.

   Case Report Top

A 6-year-old child, with steroid-resistant NS (Late resistance) for thepast two years was admitted with a relapse with peritonitis and persistent cough for 15 days. He had a fever (temperature of 102.3°F) and tachypnea (respiratory rate of 36 breaths/min) with abdominal tenderness and gross ascites. Chest examination revealed scattered crepitations over bilateral lung fields.

His illness had started at three years of age with initial steroid dependence after which he developed resistance to steroids. Renal biopsy was suggestive of minimal change disease with no chronic changes. He had been started on tacrolimus 1 mg twice daily, (tacrolimus level initially-4.2 μg/L) on which he attained complete remission and sustained it for one year. The following year, he had multiple relapses with acute kidney injury each following episodes of infection, requiring hospital admission and intermittent discontinuation of tacrolimus. He had also developed steroid-induced subcapsular cataract and hypertension [blood pressure (BP) - 122/79 mm Hg, >95th + 12 centile for age and height] requiring enalapril and calcium channel blockers. The patient was on a non–vegetarian diet, however, multiple episodes of sickness requiring hospital admission had hampered his nutrition.

During the present admission, he was started on IV antibiotics (ceftriaxone and amikacin), supportive management with albumin infusion and lasix, while tacrolimus was discontinued temporarily. On investigations, there was spontaneous bacterial peritonitis (cytology - 12000 predominantly neutrophils,protein – 91 mg/dL, sugar - 11 mg/dL) and a positive gastric aspirate for acid-fast bacilli. Contrast-enhanced computerized tomography abdomen revealed only gut wall edema.

During the days following the admission, the child developed multiple episodes of vomiting and diarrhea. The liver enzymes were normal and no microorganisms were isolated on multiple stool examinations.

Two weeks later, the child was started on full-dose steroids and tacrolimus. By now the child had been admitted to the hospital for almost five weeks and had been continuing to have intermittent vomiting and diarrhea for three weeks. He developed brisk diuresis five days after re-starting tacrolimus (4.6 mL/kg/h).

However, on day six, after starting tacrolimus, the child had one episode of abnormal movements. He had a vacant stare along with sudden shivering of all his limbs, however there was no uprolling of eyes, tonic-clonic movements, bowel bladder incontinence or tongue bite. The child became irritable following the episode. He was noted to have a high BP following this episode (BP - 142/92 mm Hg).

Laboratory investigations showed: blood gas revealed low ionized calcium (0.8 mEq/dL), serum calcium corrected for albumin was 9.9 mg/dL (serum albumin 1.02 mg/dL). Serum magnesium was 2 mEq/dL which was normal, blood sugar was 122 mg/dL. Lumbar puncture ruled out meningitis. Tacrolimus level was 3.31 μg/L, which was low. Electroencephalogram in the present case suggested evidence of intermittent generalized cerebral dysfunction with features of generalized epilepsy possibly due to metabolic encephalopathy.

Magnetic resonance imaging (MRI) of the brain revealed features of hyperintensity in bilateral thalamus involving pulvinar and ventro-medial thalami, bilateral hypothalamus, mamillary bodies, which are showing diffusion restriction-likely due to Wernicke’s encephalopathy(WE) on T2/FLAIR sequences. MR venography and angiography ruled out any intracranial thrombosis There was no evidence of PRES and no meningeal enhancement. [Figure 1]a shows diffuse cerebral atrophy with patchy hyperintensity at the medial aspect of the bilateral thalami. The coronal 3D FLAIR image (b) shows hyperintensity involving the hypothalamus. The diffusion images (c and d) and apparent diffusion coefficient (ADC) map (e) show restricted diffusion involving the medial hypothalamus, peri-ventricular region around the third ventricle, and medial thalami.
Figure 1. (a-e) Image (a-Axial T2) shows diffuse cerebral atrophy with patchy hyperintensity at the medial aspect of the bilateral thalami. The coronal 3D FLAIR image (b) shows hyperintensity involving the hypothalamus. The Diffusion images (c and d) and apparent diffusion coefficient map (e) show restricted diffusion involving the medial hypothalamus, periventricular region around the third ventricle and medial thalami (f-h): The axial T2 image (f) shows reduction in bilateral thalamic hyperintensity. Diffusion-weighted imaging (g) and ADC (h) shows minimal T2 shine through effect at both the thalami with the resolution of restricted diffusion.

Click here to view

Clinical differentials considered when dealing with the single neurological event in a child with NS on immunosuppression include, intracranial vascular thrombosis, PRES, toxicity related to use of calcineurin inhibitors, intracranial infections, i. e., meningitis and metabolic causes such as due to hypocalcemia and hypomagnesemia. Biochemistry ruled out hypocalcemia and hypomagnesemia. Microscopic examination of the cerebrospinal fluid ruled out meningitis which was confirmed on imaging. Imaging also ruled out sinus venous thrombosis, intracranial thrombosis, and PRES. Features of mammilary body enhancement seen on MRI were strongly suggestive of WE. To confirm thiamine deficiency, erythrocyte thiamine transketolase (ETKA) activity is required, however the same is not available in the clinical setting.

It is known that when the diagnosis of WE is entertained, immediate thiamine replacement takes precedence over laboratory diagnosis. A recommended regimen of 500 mg of thiamine intravenously, infused over 30 min, three times daily for two consecutive days and 250 mg intravenously or intramuscularly once daily for an additional five days, in combination with other B vitamins was administered to the child.[1]

The child’s general condition improved and irritability reduced over the next 72 h. Thiamine supplementation 100 mg once daily was continued for another six months, then stopped after documenting reversal of MRI changes. MRI was repeated four months later to look for resolution of the features. [Figure 1]f, [Figure 1]g, [Figure 1]h shows reduction in bilateral thalamic hyperintensity. Diffusion-weighted imaging (g) and ADC (h) shows minimal T2 shine through effect at both the thalami with the resolution of restricted diffusion.

The authors obtained all appropriate consent forms from the patient’s parents for the publication of this case report.

   Discussion Top

WE is an acute neuropsychiatric disorder resulting from thiamine (Vitamin B1) deficiency and characterized by a clinical triad of confusion, ocular abnormalities, and ataxia.[2]

Atrophy of the mammillary bodies is a highly specific finding in chronic WE (80% of cases).[1],[2] In the present case, these changes on MRI could not be attributed to any other medications being given to the child, like anti-tubercular therapy, steroids or tacrolimus. While clinically tacrolimus toxicity may present with seizures, it has primarily been reported among solid organ transplant recipients who receive high dose of calcineurin inhibitors, the imaging features typically described are those of PRES, and sometimes acute demyelination or leukoencephalopathy which were not seen in the present case.[3],[4]

Since the child had persistent vomiting, with a prior history of multiple relapses in a short period and sickness requiring hospital admission before the event, it is likely that the child was malnourished and persistent vomiting aggravated thiamine deficiency and led to changes that were seen on the MRI. WE may occur as early as within two to three weeks of an unhealthy diet, persistent losses like diarrhea and vomiting and in those who have sub-optimal stores, it may occur even earlier than this.[5]

Although laboratory studies and neuroimaging studies can be helpful, WE is primarily a clinical diagnosis. It is important to institute thiamine therapy as an emergency and response to treatment may be diagnostic. However, thiamine deficiency can be most reliably detected by measurement of ETKA) before and after the addition of thiamine pyrophosphate. This test is often not readily available, especially in the emergency setting. At times high performance liquid chromatography may be used.[6],[7] Thiamine levels could not be performed in the present case owing to nonavailability of the test at our center and also to the urgency of treating this condition before the child slips into overt encephalopathy.

Early detection of subclinical thiamine deficiency is challenging, because symptoms are usually nonspecific, including loss of appetite, headaches, fatigue, difficult in concentration, irritability, and abdominal discomfort. The mental status change is the most common symptom of WE and occurs in 34–82% of patients and the complete triad may be found in only 16% of the cases. The most frequently affected regions are the medial thalamus and periventricular region of the third ventricle (80%–85%), involvement of the periaqueductal area (59%–65%), mammillary bodies (38%–45%), and midbrain tectum (superior and inferior colliculi) (36%–38%) may be seen. These regions are proposed to be more sensitive to thiamine deficiency due to their high rate of thiamine-related glucose and oxidative metabolism.[8]

Though the condition is seen in alcoholics and in the elderly, this deficiency may also occur in diseases that affect children such as malignancies, intensive care unit stays, and surgical procedures. Other predisposing conditions include magnesium deficiency and defects in theSLC19A3 gene causing thiamine transporter-2 deficiency.[5] Among the pediatric population with NS only one case of a 6-year-old boy with steroid-resistant NS and who developed features of both PRES and subsequently WE have been described as the only report of WE in a child with NS in literature.[9] However, it must be emphasized that prolonged hospitalization and poor nutritional state in these children predisposes them to multivitamin deficiency and should always be kept in mind as an uncommon but readily treatable cause of encephalopathy in these children.[5],[9]

Conflict of interest: None declared.

   References Top

Cook CC, Hallwood PM, Thomson AD. B Vitamin deficiency and neuropsychiatric syndromes in alcohol misuse. Alcohol Alcohol 1998;33:317-36.  Back to cited text no. 1
Victor M, Adams RA, Collins GH. The Wernicke-Korsakoff Syndrome and Related Disorders Due to Alcoholism and Malnutrition. Philadelphia: FA Davis; 1989.  Back to cited text no. 2
Wu Q, Marescaux C, Qin X, Kessler R, Yang J. Heterogeneity of radiological spectrum in tacrolimus-associated encephalopathy after lung transplantation. Behav Neurol 2014; 2014: 931808.  Back to cited text no. 3
Chegounchi M, Hanna MG, Neild GH. Progressive neurological disease induced by tacrolimus in a renal transplant recipient: Case presentation. BMC Nephrol 2006;7:7.  Back to cited text no. 4
Lallas M, Desai J. Wernicke encephalopathy in children and adolescents. World J Pediatr 2014;10:293-8.  Back to cited text no. 5
Leigh D, McBurney A, McIlwain H. Erythrocyte transketolase activity in the Wernicke-Korsakoff syndrome. Br J Psychiatry 1981; 139:153-6.  Back to cited text no. 6
Lu J, Frank EL. Rapid HPLC measurement of thiamine and its phosphate esters in whole blood. Clin Chem 2008;54:901-6.  Back to cited text no. 7
Jung YC, Chanraud S, Sullivan EV. Neuroimaging of Wernicke’s encephalopathy and Korsakoff’s syndrome. Neuropsychol Rev 2012;22:170-80.  Back to cited text no. 8
Nishida M, Sato H, Kobayashi N, Morimoto M, Hamaoka K. Wernicke’s encephalopathy in a patient with nephrotic syndrome.Eur J Pediatr2009;168:731-4.  Back to cited text no. 9

Correspondence Address:
Aliza Mittal
Department of Pediatrics, All India Institute of Medical Sciences, Jodhpur, Rajasthan
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.344767

Rights and Permissions


  [Figure 1]


    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report
    Article Figures

 Article Access Statistics
    PDF Downloaded41    
    Comments [Add]    

Recommend this journal