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 Table of Contents  
Year : 2021  |  Volume : 8  |  Issue : 1  |  Page : 47-49

Acute necrotizing encephalopathy of childhood: Not always devastating

1 Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Division of Pediatric Neurology, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Submission27-Aug-2020
Date of Decision11-Sep-2020
Date of Acceptance25-Sep-2020
Date of Web Publication08-Jan-2021

Correspondence Address:
Dr. Suresh Kumar Angurana
Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JPCC.JPCC_139_20

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Acute necrotizing encephalopathy of childhood (ANEC) is an uncommon cause of acute onset febrile encephalopathy, which progresses rapidly and has poor outcomes. We reported a 4-year-old female who presented with acute febrile encephalopathy, raised intracranial pressure (ICP), and respiratory failure. The brain imaging was suggestive of ANEC. The treatment included antibiotics, antivirals, mechanical ventilation, measures to lower ICP, intravenous immunoglobulin, and supportive care in the Pediatric intensive care unit with which she made a remarkable recovery.

Keywords: Encephalopathy, intravenous immunoglobulin, raised intracranial pressure, thalamus

How to cite this article:
Kumar S, Kumar V, Singanamalla B, Vyas S, Angurana SK. Acute necrotizing encephalopathy of childhood: Not always devastating. J Pediatr Crit Care 2021;8:47-9

How to cite this URL:
Kumar S, Kumar V, Singanamalla B, Vyas S, Angurana SK. Acute necrotizing encephalopathy of childhood: Not always devastating. J Pediatr Crit Care [serial online] 2021 [cited 2021 Apr 20];8:47-9. Available from: http://www.jpcc.org.in/text.asp?2021/8/1/47/306482

  Introduction Top

Acute necrotizing encephalopathy of childhood (ANEC) is a severe debilitating neurological disorder characterized by progressive encephalopathy, seizures and associated with high morbidity and mortality. Viruses are the most common etiology of ANEC with influenza and human herpes virus-6 (HHV-6) being the commonest.[1],[2],[3] The neurological damage is possibly due to direct viral injury, immune-mediated injury, or cytokine storm.[1],[2],[4] The classical neuroradiological findings of ANEC include bilateral symmetrical involvement of the thalamus, internal capsule, putamen, cerebellum, brainstem, and periventricular white matter; and trilaminar pattern of the thalamus on apparent diffusion coefficient (ADC) images.[5],[6],[7] In the absence of standard guidelines, the commonly used treatment modalities include antiviral drugs, intravenous immunoglobulin (IVIG), steroids (methylprednisolone or dexamethasone), plasmapheresis, antithrombin III, and therapeutic hypothermia.[1],[2] The literature about ANEC is limited and mostly reported poor neurological outcome.[8],[9] The remarkable recovery in index child with ANEC made us to report this case.

  Case Report Top

A 4-year-old female presented with fever for 5 days and generalized tonic-clonic seizures and altered sensorium for 2 days. There was no history of recent travel, vaccination, dog bite, herpes simplex infection or varicella, and no past illness. Examination revealed weight 17 kg, pulse rate 92/min, respiratory rate 30/min, palpable central and peripheral pulses, SpO2 95%, and blood pressure 110/80 mmHg. Central nervous system examination revealed Glasgow Coma Scale of 8, increased tone with intermittent decerebrate posturing, brisk deep tendon reflexes, extensor plantar reflexes, normal-sized pupil with normal reaction to light, no signs of meningeal irritation, and normal fundus examination. The liver was enlarged with a span of 10 cm. The examination of other systems was normal.

She was intubated and started on mechanical ventilation, maintenance intravenous fluids, antibiotic (intravenous ceftriaxone and acyclovir), antiepileptic drugs (phenytoin followed by levetiracetam), sedation and analgesia (midazolam and fentanyl) infusion, head-end elevation by 30°, head in midline, and 3% saline bolus (5 ml/kg) followed by infusion (0.5 ml/kg/h).

Investigations revealed hemoglobin 9.1 g/dL, total leukocyte count 13,570/cumm, platelet count 370,000/cumm, international normalized ratio 1.2, sodium 146 meq/L, potassium 4.6 meq/L, urea 18 mg/dL, creatinine 0.3 mg/dL, serum glutamic-oxaloacetic transaminase 360 IU/L, serum glutamic pyruvic transaminase 320 IU/L, total protein 6.7 g/dL, albumin 35 g/dL, bilirubin 0.3 mg/dL, and serum ammonia 45 μmol/L. Noncontrast and contrast-enhanced computed tomography head on day 1 revealed poor grey-white matter differentiation and chinked ventricles without any meningeal enhancement. NS1 antigen and dengue IgM antibody, nasopharyngeal swab for H1N1, herpes simplex virus (HSV) serology, JE serology, and mycoplasma serology were negative. Cerebrospinal fluid (CSF) analysis was done on day 4 revealed no cells, glucose 75 mg/dL, protein 104 mg/dL, and negative HSV DNA polymerase chain reaction.

Magnetic resonance imaging (MRI) brain was performed on day 5 of admission, which revealed ill-defined areas of altered signal intensity involving thalami and bilateral frontoparietal regions, which were hypointense on T1 and hyperintense on T2 weighted and fluid-attenuated inversion recovery images [Figure 1]. Based on the temporal evolution of the clinical symptoms, laboratory investigations, and MRI findings, a diagnosis of ANEC was made. The treatment addition included azithromycin, oseltamivir, and IVIG (2 g/kg over 48 h). She developed ventilator-associated pneumonia due to Acinetobacter baumannii on day 5, which was treated with colistin. There was a gradual improvement in respiratory and neurological status. She was weaned from mechanical ventilation extubated on day 11 of the PICU stay. She was discharged on day 14 with normal neurological examination and pediatric cerebral performance category score of 2.
Figure 1: Axial T2 (a and d), fluid-attenuated inversion recovery (b and e) and T1 (c and f) magnetic resonance images showing altered signal intensity lesions in form of T2/fluid-attenuated inversion recovery hyper-intensities and T1 hypo-intensities involving bilateral thalami (black arrows) and periventricular white matter, more so in fronto-parietal region (white arrows). No diffusion restriction or susceptibility changes seen in these areas

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  Discussion Top

We described a child with ANEC who recovered remarkably with treatment in the form of antibiotics, antivirals, antiepileptics, mechanical ventilation, management of raised intracranial pressure, IVIG, and supportive care. ANEC is an uncommon severe debilitating neurological disorder sporadically affect previously healthy infants and children, causing rapid progressive encephalopathy, seizures, and poor outcome.[1],[9] The etiology of ANEC is not clearly known, but viruses are most commonly implicated, including influenza virus, HHV-6, parainfluenza, varicella-zoster virus, human HHV-7, enterovirus, reovirus, rotavirus, HSV, rubella, coxsackie A9, and measles. Other causes include mycoplasma, immune-mediated, and genetic (RANBP2 mutation).[1],[2],[3] The neurological damage occurs due to an immune-mediated injury or cytokine storm, leading to damage to blood-brain barrier in particular regions of the brain, resulting in localized edema, congestion, hemorrhage, and necrosis without any signs of direct viral invasion or post-infectious demyelination.[1],[2],[4]

The classical radiological findings of ANEC include bilateral symmetrical involvement of the thalamus. Other topographical involvement includes multifocal, symmetric brain lesions involving both the grey and white matter, internal capsule, putamen, cerebellum, brainstem, periventricular white matter, and occasionally spinal cord.[2],[5],[10] The characteristic involvement of thalamus is seen in the form of trilaminar, target or tricolor pattern on ADC images which occurs due to central hemorrhage and necrosis, surrounded by cytotoxic edema and vascular congestion, and peripheral vasogenic edema.[6],[7] Wong et al. devised a composite score for patients with ANEC and observed a positive correlation between the MRI brain findings and clinical outcomes.[11] In survivors, the follow-up imaging had shown significant resolution of lesions with some residual changes such as cortical atrophy, cystic changes, and hemosiderin deposition.[1],[2]

Mizuguchi proposed criteria for the diagnosis of typical ANEC. It included the acute onset of encephalopathy (following a viral illness) with rapid deterioration in neurological status; increased protein with no pleocytosis on CSF examination; neuroimaging showing bilateral symmetrical involvement of the thalamus, internal capsule, putamen, cerebellum, brainstem, and periventricular white matter; normal blood ammonia; elevated serum transaminases; and exclusion of other viral or bacterial infections, Reye's syndrome, Leigh disease, acute disseminated encephalomyelitis(ADEM), and vasculitis.[5] The index child had the majority of these features, except we did not test her for mitochondrial disorders and vasculitis. Furthermore, there may be cellular response in a few children, as noted by Chow and Ma in 1 out of 8 episodes of ANEC in 7 children.[10]

Though there are no standard guidelines for the treatment of ANEC, the commonly used treatment modalities include antiviral drugs, IVIG, steroids (methylprednisolone or dexamethasone), plasmapheresis, antithrombin III, and therapeutic hypothermia.[1],[2],[10],[12] In children with ANEC, the morbidity and mortality are high and complete recovery is seen in <10% cases.[8],[9] The index child was treated with antiviral drugs, mechanical ventilation, IVIG, and supportive care and had recovered with the normal neurological examination at discharge.

  Conclusion Top

The ANEC is uncommon neurological disorder with high morbidity and mortality. The aggressive supportive treatment and immunomodulatory treatment may lead to a remarkable recovery.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Yoganathan S, Sudhakar SV, James EJ, Thomas MM. Acute necrotising encephalopathy in a child with H1N1 influenza infection: a clinicoradiological diagnosis and follow-up. BMJ Case Rep. 2016 Jan 11;2016:bcr2015213429. doi: 10.1136/bcr-2015-213429.  Back to cited text no. 1
Wu X, Wu W, Pan W, Wu L, Liu K, Zhang HL. Acute necrotizing encephalopathy: an underrecognized clinicoradiologic disorder. Mediators Inflamm. 2015;2015:792578. doi: 10.1155/2015/792578.  Back to cited text no. 2
Takia L, Saini L, Keshavan S, Angurana SK, Nallasamy K, Suthar R, et al. Neurological Manifestations of Influenza A (H1N1): Clinical Features, Intensive Care Needs, and Outcome. Indian J Pediatr 2020;87:803-9.  Back to cited text no. 3
Kansagra SM, Gallentine WB. Cytokine storm of acute necrotizing encephalopathy. Pediatr Neurol 2011;45:400-2.  Back to cited text no. 4
Mizuguchi M. Acute necrotizing encephalopathy of childhood: A novel form of acute encephalopathy prevalent in Japan and Taiwan. Brain Dev 1997;19:81-92.  Back to cited text no. 5
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. 6
Biswas A, Varman M, Gunturi A, Yoganathan S, Gibikote S. Teaching neuroimages: Acute necrotizing encephalopathy of childhood: Neuroimaging findings. Neurology 2018;90:e177-78.  Back to cited text no. 7
Mizuguchi M. [Acute necrotizing encephalopathy of childhood]. Ryoikibetsu Shokogun Shirizu. 2000;(30 Pt 5):527-30. Japanese.  Back to cited text no. 8
Lim HY, Ho VP, Lim TC, Thomas T, Chan DW. Serial outcomes in acute necrotising encephalopathy of childhood: A medium and long term study. Brain Dev 2016;38:928-36.  Back to cited text no. 9
Chow CK, Ma CK. Presentation and outcome of acute necrotizing encephalopathy of childhood: A 10-year single-center retrospective study from Hong Kong. J Child Neurol 2020;35:674-80.  Back to cited text no. 10
Wong AM, Simon EM, Zimmerman RA, Wang HS, Toh CH, Ng SH. Acute necrotizing encephalopathy of childhood: Correlation of MR findings and clinical outcome. AJNR Am J Neuroradiol 2006;27:1919-23.  Back to cited text no. 11
Okumura A, Mizuguchi M, Kidokoro H, Tanaka M, Abe S, Hosoya M, et al. Outcome of acute necrotizing encephalopathy in relation to treatment with corticosteroids and gammaglobulin. Brain Dev 2009;31:221-7.  Back to cited text no. 12


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