J Korean Med Sci.  2010 Mar;25(3):449-453. 10.3346/jkms.2010.25.3.449.

Clinical Spectrum and Prognostic Factors of Acute Necrotizing Encephalopathy in Children

• Seo HE
• Hwang SK
• Choe BH
• Cho MH
• Park SP
• Kwon S

• KMID: 1778042
• DOI: http://doi.org/10.3346/jkms.2010.25.3.449

Abstract

This study was conducted to investigate the etiology, the clinical characteristics and prognosis of acute necrotizing encephalopathy (ANE) in Korean children. Six children (1 yr to 7 yr) patients with ANE were enrolled. They were diagnosed by clinical and radiological characteristics and their clinical data were retrospectively analyzed. In a search of clinically plausible causes, brain MRI in all patients, mitochondrial DNA studies for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) and myoclonus epilepsy and ragged red fibers (MERRF) in four patients, and genomic typing on HLA DRB/HLA DQB genes in three patients were performed. All had precedent illnesses and the main initial symptoms included mental change (83%), seizures (50%), and focal deficits (50%). MRI revealed increased T2 signal density in the bilateral thalami and/or the brainstem in all patients. Mitochodrial DNA studies for MELAS and MERRF were negative in those children and HLA-DRB1*1401, HLA-DRB3*0202, and HLA-DQB1*0502 seemed to be significant. A high dose steroid was given to all patients, which seemed to be partly effective except for 2 patients. In conclusion, ANE is relatively rare, but can result in serious neurological complication in children. Early detection and appropriate treatment may lead to a better neurological outcome.

Keyword

Acute Necrotizing Encephalopathy; Mitochodrial; MELAS Syndrome; MERRF Syndrome; HLA-DR Antigens; HLA-DQ Antigens

MeSH Terms

Child
Child, Preschool
Female
HLA-DQ Antigens/metabolism
HLA-DQ beta-Chains
HLA-DR Antigens/metabolism
HLA-DRB1 Chains
HLA-DRB3 Chains
Humans
Infant
Korea
Leukoencephalitis, Acute Hemorrhagic/diagnosis/etiology/*pathology/*physiopathology
MELAS Syndrome/pathology/physiopathology
MERRF Syndrome/pathology/physiopathology
Magnetic Resonance Imaging
Male
Prognosis
Retrospective Studies
HLA-DQ Antigens
HLA-DQ beta-Chains
HLA-DR Antigens
HLA-DRB1 Chains
HLA-DRB3 Chains

Figure

• 

  Fig. 1 Radiological findings in a patient with ANE. (A) MRI shows symmetric, multifocal brain lesions involving bilateral thalami and upper brain stem tegmentum without involvement of other CNS regions. (B) Follow-up MRI shows complete resolution of previous lesions.

Reference

1. Mizuguchi M. Acute necrotizing encephalopathy in childhood: a novel form of acute encephalopathy prevalent in Japan and Taiwan. Brain Dev. 1997. 19:81–92.

2. Mizuguchi M, Abe J, Mikkaichi K, Noma S, Yoshida K, Yamanaka T, Kamoshita S. Acute necrotising encephalopathy of childhood: a new syndrome presenting with multifocal, symmetric brain lesions. J Neurol Neurosurg Psychiatry. 1995. 58:555–561.

3. San Millan B, Teijeira S, Penin C, Garcia JL, Navarro C. Acute necrotizing encephalopathy of childhood: report of a spanish case. Pediatr Neurol. 2007. 37:438–441.

4. Yoshikawa H, Watanabe T, Abe T, Oda Y. Clinical diversity in acute necrotizing encephalopathy. J Child Neurol. 1999. 14:249–255.

5. Yagishita A, Nakano I, Ushioda T, Otsuki N, Hasegawa A. Acute encephalopathy with bilateral thalamotegmental involvement in infants and children: imaging and pathology findings. Am J Neuroradiol. 1995. 16:439–447.

6. Mastroyianni S, Gionnis D, Voudris K, Skardoutsou A, Mizuguchi M. Acute necrotizing encephalopathy of childhood in non-Asian patients: report of three cases and literature review. J Child Neurol. 2006. 21:872–879.

7. Olgar S, Ertugrul T, Nisli K, Aydin K, Caliskan M. Influenza A associated acute necrotizing encephalopathy. Neuropediatrics. 2006. 37:166–168.

8. Okumura A, Kidokoro H, Mizuguchi M, Kurahashi H, Hirabayashi Y, Morishima T, Watanabe K. The mildest form of acute necrotizing encephalopathy associated with influenza A. Neuropediatrics. 2006. 37:261–263.

9. Grose C. The puzzling picture of acute necrotizing encephalopathy after influenza A and B virus infection in young children. Pediatr Infect Dis J. 2004. 23:253–254.

10. Ohasaka M, Houkin K, Takigami M, Koyanagi I. Acute necrotizing encephalopathy associated with human herpesvirus-6 infection. Pediatr Neurol. 2006. 34:160–163.

11. Skelton BW, Hollingshead MC, Sledd AT, Phillips CD, Castillo M. Acute necrotizing encephalopathy of childhood: typical findings in an atypical disease. Pediatr Radiol. 2008. 38:810–813.

12. Tran TD, Kubota M, Takeshita K, Yanagisawa M, Sakakihara Y. Varicella-associated acute necrotizing encephalopathy with a good prognosis. Brain Dev. 2001. 23:54–57.

13. Kirton A, Busche K, Ross C, Wirrell E. Acute necrotizing encephalopathy in Caucasian children: two cases and review of the literature. J Child Neurol. 2005. 20:527–532.

14. Ashtekar CS, Jaspan T, Thomas D, Weston V, Gayatri NA, Whitehouse WP. Acute bilateral thalamic necrosis in a child with Mycoplasma pneumonia. Dev Med Child Neurol. 2003. 45:634–637.

15. Libert UG, Schneider-Schaulies S, Baczko K, ter Meulen V. Antibody-induced restriction of viral gene expression in measles encephalitis in rat. J Virol. 1990. 64:706–713.

16. Chou HF, Liang WC, Zhang Q, Goto Y, Jong YJ. Clinical and genetic features in a MELAS child with a 3271T>C mutation. Pediatr Neurol. 2008. 38:143–146.

17. Qi Y, Zhang Y, Wang Z, Yang Y, Yuan Y, Niu S, Pei P, Wang S, Ma Y, Bu D, Zou L, Fang F, Xiao J, Sun F, Zhang Y, Wu Y, Wang S, Xiong H, Wu X. Screening of common mitochondrial mutations in Chinese patients with mitochondrial encephalomyopathies. Mitochondrion. 2007. 7:147–150.

18. Oh HH, Kwon SH, Kim CW, Choe BH, Ko CW, Jung HD, Suh JS, Lee JH. Moelcular anaysis of HLA Class II-associated susceptibility to neuroinflammatory disease in Korean children. J Korean Med Sci. 2004. 19:426–430.

19. Kim JH, Kim IO, Lim MK, Park MS, Choi CG, Kim HW, Kim JE, Choi SJ, Koh YH, Yang DM, Choo SW, Chung MJ, Yoon HK, Goo HW, Lee M. Acute necrotizing encephalopathy in Korean infants and children: imaging findings and diverse clinical outcome. Korean J Radiol. 2004. 5:171–177.

20. Goo HW, Choi CG, Yoon CH, Ko TS. Acute necrotizing encephalopathy: diffusion MR imaging and localized proton MR spectroscopic findings in two infants. Korean J Radiol. 2003. 4:61–65.

21. Ichiyama T, Endo S, Kaneko M, Isumi H, Matsubara T, Furukawa S. Serum cytokine concentration of influenza-associated acute necrotizing encephalopathy. Pediatr Int. 2003. 45:734–736.

22. Okumura A, Mizuguchi M, Kidokoro H, Tanaka M, Abe S, Hosoya M, Aiba H, Maegaki Y, Yamamoto H, Tanabe T, Noda E, Imataka G, Kurahashi H. Outcome of acute necrotizing encephalopathy in relation to treatment with corticosteroids and gammaglobulin. Brain Dev. 2009. 31:221–227.

23. Akiyoshi K, Hamada Y, Yamada H, Kojo M, Izumi T. Acute necrotizing encephalopathy associated with hemophagocytic syndrome. Pediatr Neurol. 2006. 34:315–318.

24. Manara R, Franzoi M, Cogo P, Battistella PA. Acute necrotizing encephalopathy: combined therapy and favorable outcome in a new case. Childs Nerv Syst. 2006. 22:1231–1236.

25. 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. 27:1919–1923.