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Year : 2023  |  Volume : 10  |  Issue : 3  |  Page : 121-123

Acute necrotizing encephalopathy of childhood as a complication of dengue infection: A case report

Department of Paediatrics, Government Medical College, Jammu, Jammu and Kashmir, India

Date of Submission09-Feb-2023
Date of Decision20-Mar-2023
Date of Acceptance28-Mar-2023
Date of Web Publication19-May-2023

Correspondence Address:
Dr. Mohammad Irfan Dar
Department of Paediatrics, Government Medical College, Jammu, Jammu and Kashmir
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcc.jpcc_10_23

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Acute necrotizing encephalopathy of childhood (ANEC) is a clinico-radiological diagnosis characterized by acute onset, and progressive febrile encephalopathy preceded by viral-associated febrile illness and carries a very poor prognosis. We present a case of 9-year-old child with dengue virus-induced necrotizing encephalopathy who was managed with pulse methylprednisolone therapy followed by oral prednisolone. The rarity of ANEC in association with dengue and good neurological recovery with supportive treatment made us to report this case.

Keywords: Acute necrotizing encephalopathy of childhood, acute necrotizing encephalopathy, dengue

How to cite this article:
Dar MI, Bhat V, Bhardwaj S. Acute necrotizing encephalopathy of childhood as a complication of dengue infection: A case report. J Pediatr Crit Care 2023;10:121-3

How to cite this URL:
Dar MI, Bhat V, Bhardwaj S. Acute necrotizing encephalopathy of childhood as a complication of dengue infection: A case report. J Pediatr Crit Care [serial online] 2023 [cited 2023 Jun 2];10:121-3. Available from: http://www.jpcc.org.in/text.asp?2023/10/3/121/377431

  Introduction Top

Acute necrotizing encephalopathy of childhood (ANEC) is a clinico-radiological diagnosis seen in previously healthy children. It is predominantly seen in children and adolescents with characteristic imaging finding of bilateral, symmetrical necrotic lesion of thalami and other brain regions. Clinically, a patient presents with acute onset and rapidly progressive febrile encephalopathy preceded by viral-associated febrile illness.[1] Acute necrotizing encephalitis carries a very poor prognosis; the mortality rate is near 70%.[2] It is caused by parainfectious, triggers mainly viruses including influenza, human herpesvirus 6, parainfluenza, human herpesvirus 7, varicella, enterovirus, flaviviruses, rotavirus, herpes simplex virus, rubella, coxsackie A9, and measles.[3],[4]

  Case Report Top

A 9-year-old boy was referred to pediatric emergency with a history of altered sensorium for 1 day. Previously, the child had a history of fever for 4 days followed by two episodes of vomiting and two episodes of abnormal body movements on 4th day of illness followed by altered sensorium on 5th day of illness. Fever was absent from day 4 of illness and the child was managed as dengue with warning signs at peripheral hospital but was referred to tertiary care hospital after altered sensorium and two episodes of seizures. At peripheral hospital, investigations revealed thrombocytopenia (118,000/cmm) and positive NS1Ag for dengue.

On examination, the child was sick looking, lethargic euthermic, respiratory rates 30/min, cold peripheries, low volume pulse, and blood pressure 96/58 mmHg. Central nervous examination revealed low Glasgow Coma Scale (9/15), brisk deep tendon reflexes, positive Babinski reflex, and Brudzinski's sign. The child initially received fluid blouses (total 40 mL per kg) in emergency triage room and was shifted to pediatric intensive care unit (PICU) for further management.

In PICU, the child was managed as expanded dengue syndrome (dengue encephalitis) and received intravenous antibiotics (ceftriaxone and phenytoin) with measures to lower raised intracranial pressure.

Investigations revealed blood glucose 115 mg/dL, hemoglobin 10.1 g/dL, total leukocyte count 12,700/cumm, platelet count 170,000/cumm, serum sodium 136 meq/L, potassium 3.9 meq/L, urea 16 mg/dL, creatinine 0.5 mg/dL, bilirubin 0.4 mg/dL, serum glutamic-oxaloacetic transaminase 435 IU/L, serum glutamate-pyruvate transaminase 480 IU/L, protein 6.4 g/dL, and albumin 3.5 g/dL. Noncontrast computed tomography head [Figure 1] revealed hypodensities involving bilateral thalami, internal capsule left midbrain and pons and left middle and inferior cerebella's peduncle. Cerebrospinal fluid (CSF) analysis revealed 13 cells/cumm (30% neutrophils and 70% lymphocytes), protein 94 mg%, and glucose 75 mg%, and sterile culture and dengue immunoglobulin M antibodies were positive in blood.
Figure 1: Noncontrast CT head showing hypodensities in bilateral thalami. CT: Computed tomography

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The child was diagnosed with acute necrotizing encephalopathy and was started on pulse methylprednisolone therapy (30 mg/kg) for 5 days followed by oral prednisolone at 2 mg/kg/day. The child showed improvement in sensorium after receiving second dose of pulse therapy. Oxygen was stopped on 3rd day in PICU. Bladder control was achieved on day 6th of hospitalization and ryles tube was removed on 7th day of admission. Liver function tests improved within 1 week of hospitalization.

Magnetic resonance imaging (MRI) brain was done on 8th day of admission (14th day of illness) which revealed an altered signal intensity lesion involving bilateral thalami appearing hypointense on T1, hyperintense on T2/fluid-attenuated inversion-recovery with areas of restricted diffusion, and central blooming on susceptibility-weighted imaging. Mild edema was noted in adjacent posterior limb of the internal capsule and bilateral lentiform nuclei. T2 hyperintensity with multiple foci of blooming was noted involving the dorsal aspect of pons [Figure 2]. Impression of MRI report was encephalitis likely induced by flavivirus.
Figure 2: MRI brain (FLAIR and T2) showing symmetrical hyperintensities in bilateral thalamic region. MRI: Magnetic resonance imaging, FLAIR: Fluid-attenuated inversion-recovery

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The child was discharged on day 10th of illness and was followed up for 4 weeks, and oral prednisolone was given for 2 weeks and tapered in the next 2 weeks. The child was followed up regularly for 3 months and showed no residual weakness in none of the domains and is attending his school normally.

  Discussion Top

ANEC is a rapidly progressive encephalopathy affecting infants and children first described among Japanese and Taiwanese patients by Mizuguchi in 1995. Most of the cases have been identified from South East Asia. Diagnostic criteria of ANEC as described by Mizuguchi are: (1) encephalopathy preceded by viral febrile illness with rapid deterioration in the level of consciousness and convulsions, (2) absent CSF pleocytosis, (3) symmetric multifocal brain lesions, (4) elevation in serum aminotransferase levels, and (5) exclusion of similar diseases.[5]

The exact pathogenesis of ANEC is still not clear. The most prevalent hypothesis is the increased cytokine levels causing “cytokine storm” resulting in brain injury by altering vessel wall permeability without vessel wall disruption or inflammation; shock, liver dysfunction, acute renal failure, and disseminated intravascular coagulation.[6] ANEC is not considered inflammatory encephalitis due to the minimal inflammation in histopathological studies compared to marked necrosis and also the absence of CSF pleocytosis in most cases. Genetic predisposition has been noted, especially in familial and recurrent cases. Ran binding protein 2 is one such gene, missense mutations predispose to ANEC in autosomal dominant pattern with incomplete penetrance with some cases occurring without infectious trigger.[7]

Bilateral, symmetrical brain lesions involving thalamus, brain stem, cerebrum, and cerebellum affecting both gray and white matter with necrosis and hemorrhage is the characteristic feature of ANEC. Thalamus is involved in most of the cases along with involvement of brain stem, cerebral, and cerebellar white matter. The pattern of thalamic involvement is the hallmark of ANEC aiding in clinching the diagnosis.[1] The trilaminar pattern is the hallmark pattern of involvement which is best seen in apparent diffusion coefficient (ADC) image with higher than normal ADC values at the center of lesion due to hemorrhage, surrounded by low ADC values at the peripheral portion of central lesions suggesting cytotoxic edema with very high ADC value at the outermost region suggesting vasogenic edema.[3] Gradient echo imaging shows blooming in central of lesion with surrounding hyperintensity of swollen thalami. Similar pattern has been described in dengue encephalitis as double doughnuts sign by Kumar et al.[8] ANE due to genetic causes may have atypical radiological involvement with additional MRI changes in the medial temporal lobes, external capsule, claustrum, insular cortices, hippocampi, amygdala, mammillary, and spinal cord with some cases without thalamic involvement.[3]

There are no standard guidelines for the treatment of ANEC, the commonly used modalities include steroids, intravenous immunoglobulins (IVIGs), plasmapheresis, antithrombin III, and therapeutic hypothermia. Most often, the children with ANEC are managed with the administration of steroids ± IVIG, but due to financial constraints of the family, only pulse steroid therapy was given in this case. Administration of steroids within 24 h of onset of encephalopathy has shown better outcomes in children as compared to IVIG with ANEC without brain stem lesions.[9]

Although studies have shown benefit of steroids in the management of ANEC literature is not enough to formulate recommendations for the management of this disease.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's legal guardian has given the consent for images and other clinical information to be reported in the journal. The patient's legal guardian understands that name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Albayram S, Bilgi Z, Selcuk H, Selcuk D, Cam H, Koçer N, et al. Diffusion-weighted MR imaging findings of acute necrotizing encephalopathy. AJNR Am J Neuroradiol 2004;25:792-7.  Back to cited text no. 1
St-Amant M, Najjar R, Fortin F, Muzio BD, Glick Y, Yap J, et al. Acute necrotizing encephalopathy. Reference article, Radiopaedia.org https://doi.org/10.53347/rID-24838. Available from: https://radiopaedia.org/articles/24838 [Last accessed on 2023 Feb 09].  Back to cited text no. 2
Holla VV, Gohel AB, Kartik N, Netravathi M. Acute necrotizing encephalopathy as a complication of Chikungunya infection. Neurol India 2021;69:490-2.  Back to cited text no. 3
[PUBMED]  [Full text]  
Abbas Q, Jafri SK, Ishaque S, Jamil MT. Acute necrotizing encephalopathy of childhood secondary to dengue infection: A case report from Pakistan. J Pediatr Neurosci 2017;12:165-7.  Back to cited text no. 4
[PUBMED]  [Full text]  
Mizuguchi M, Abe J, Mikkaichi K, Noma S, Yoshida K, Yamanaka T, et al. Acute necrotising encephalopathy of childhood: A new syndrome presenting with multifocal, symmetric brain lesions. J Neurol Neurosurg Psychiatry 1995;58:555-61.  Back to cited text no. 5
Kansagra SM, Gallentine WB. Cytokine storm of acute necrotizing encephalopathy. Pediatr Neurol 2011;45:400-2.  Back to cited text no. 6
Neilson DE, Adams MD, Orr CM, Schelling DK, Eiben RM, Kerr DS, et al. Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2. Am J Hum Genet 2009;84:44-51.  Back to cited text no. 7
Kumar AS, Mehta S, Singh P, Lal V. Dengue encephalitis: “Double doughnut” sign. Neurol India 2017;65:670-1.  Back to cited text no. 8
[PUBMED]  [Full text]  
Kumar S, Navid A, Sharma R, Suthar R, Vyas S, Angurana SK. Acute necrotizing encephalopathy of childhood: A rare neurological manifestation of dengue. Ann Indian Acad Neurol 2021;24:828-31.  Back to cited text no. 9
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