Acute Necrotizing Encephalopathy in Caucasian Children: Two Cases and Review of the Literature

Abstract

Acute necrotizing encephalopathy is a fulminant neurologic disease seen predominantly in Japan and Taiwan. We present two cases diagnosed at a Canadian center within the same year in Caucasian children. Both were previously well, developed an acute viral illness with fever and vomiting, and progressed to brain death within 2 to 4 days. Neuroimaging and postmortem examination demonstrated the unique features of bilateral and severe necrosis of deep gray-and subcortical white-matter structures. The first case was associated with extensive, but transient, hepatic involvement, recent varicella and rotavirus infections, and detailed metabolic studies, including mitochondrial functional analysis, were normal. The second case tested positive for influenza A infection, whereas evidence of liver damage was lacking. Both children demonstrated early lymphopenia and myocardial necrosis, two features not previously associated with acute necrotizing encephalopathy. These cases are unique in their occurrence in non-Japanese children and are among the first published reports in Canada. (J Child Neurol 2005;20:527—532).

Get full access to this article

View all access options for this article.

References

Mizuguchi M. , Abe J. , Mikkaichi L. , et al: Acute necrotizing encephalopathy of childhood: A new syndrome presenting with multifocal, symmetric brain lesions . J Neurol Neurosurg Psychiatry 1995;58:555—561.

Charney EB , Orecchio EJ , Zimmerman RA , et al: Computerized tomography in infantile encephalitis. Am J Dis Child 1979;133:803—805.

Protheroe S. , Mellor D. : Imaging in influenza A encephalitis. Arch Dis Child 1991;66:702—705.

Pedro VJ , Lobo AN , Levy GA : Acute infantile thalamic necrosis. Dev Med Child Neurol 1995;37:1006—1019.

Campistol J. , Gassio R. , Pineda M. , Fernandez-Alvarez E. : Acute necrotizing encephalopathy of childhood (infantile bilateral thalamic necrosis): Two non-Japanese cases . Dev Med Child Neurol 1998;40:771—774.

Porto L. , Lanferman H. , Moller-Hartmann W. , et al: Acute necrotizing encephalopathy of childhood after exanthema subitum outside Japan or Taiwan. Neuroradiology 1999;41:732—734.

Ravid S. , Topper L. , Eviatar L. : Acute necrotizing encephalopathy presenting as a basal ganglia syndrome. J Child Neurol 2001;16:461—462.

Voudris KA , Skaadoutsou A. , Haronitis I. , et al: Brain MRI findings in influenza A-associated acute necrotizing encephalopathy of childhood. Eur J Paediatr Neurol 2001;5:199—202.

Bassuk AG , Burrowes DM , McRae W. : Acute necrotizing encephalopathy of childhood with radiographic progression over 10 hours. Neurology 2003;60:1552—1553.

10.

Sazgar M. , Robinson JL , Chan Akj , Sinclair DB : Influenza B acute necrotizing encephalopathy: A case report and literature review. Pediatr Neurol 2003;28:396—399.

11.

Fujimoto Y. , Shibata M. , Tsuyuki M. , et al: Influenza A virus encephalopathy with symmetrical thalamic lesions. Eur J Pediatr 2000;159:319—321.

12.

Munakata M. , Kato R. , Yokoyama HJ , et al: Combined therapy with hypothermia and anticytokine agents in influenza A encephalopathy. Brain Dev 2000;22:373—377.

13.

Sugaya N. : Influenza-associated encephalopathy in Japan: Pathogenesis and treatment. Pediatr Int 2000;42:215—218.

14.

Shinjoh M. , Bamba M. , Jozaki K. , et al: Influenza A-associated encephalopathy with bilateral thalamic necrosis in Japan. Clin Infect Dis 2000;31:611—613.

15.

Oki J. , Yoshida H. , Tokumitsu A. , et al: Serial neuroimaging of acute encephalopathy associated with human herpes virus 6 infection. Brain Dev 1995;17:356—359.

16.

Mizuguchi M. : Acute necrotizing encephalopathy of childhood: A novel form of acute encephalopathy prevalent in Japan and Taiwan. Brain Dev 1997;19:81—92.

17.

Tuan TD , Kubota M. , Takeshita K. , et al: Varicella-associated acute necrotizing encephalopathy with a good prognosis. Brain Dev 2001;23:54—57.

18.

Yoshikawa H. , Watanabe T. , Oda Y. : Selective, reversible thalamic involvement with influenza A infection. Pediatrics 1998 ;102:1494—1495.

19.

Kimura S. , Ohtuki N. , Nezu A. , et al: Clinical and radiological variability of influenza-related encephalopathy or encephalitis. Acta Pediatr Jpn 1998;40:264—270.

20.

Saito T. , Chikumaru Y. , Koriyama T. , et al: [A case of acute necrotizing encephalopathy of childhood with a good outcome]. No To Hattatsu 1998;30:398—402.

21.

Togashi T. , Matsuzono Y. , Narita M. : Epidemiology of influenza-associated encephalitis-encephalopathy in Hokkaido, the northern most island of Japan. Pediatr Int 2000;42:192—196.

22.

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

23.

Nolte KB , Alakija P. , Oty G. , et al: Influenza A virus infection complicated by fatal myocarditis. Am J Forensic Med Pathol 2000;21:375—379.

24.

Kalita J. , Misura UK : Comparison of CT scan and MRI findings in the diagnosis of Japanese encephalitis . J Neurol Sci 2000;174:3—8.

25.

Hyun WG , Choong-gon C. , Chong HY , Tae-Sung K: Acute necrotizing encephalopathy: Diffusion MR imaging and localized spectroscopic findings in two infants. Korean J Radiol 2003;4:61—5.

26.

Miziguchi M. , Hayashi M. , Nakano I. , et al: Concentric structure of thalamic lesions in acute necrotizing encephalopathy. Neuroradiology 2002;44:489—493.

27.

Sugaya N. : Influenza-associated encephalopathy in Japan. Semin Pediatr Infect Dis 2002;13:79—84.

28.

Neilson DE , Eiben RM , Waniewski S. , et al: Autosomal dominant acute necrotizing encephalopathy. Neurology 2003;61:226—230.

29.

Neilson DE , Feiler HS , Wilhelmsen KC , et al: Autosomal dominant acute necrotizing encephalopathy maps to 2q12.1-2q13. Ann Neurol 2004;55:291—294.

30.

DeVivo DC : Leigh syndrome: Historical perspective and clinical variation. Biofactors 1998;7:269—271.

31.

Ruggieri M. , Polizzi A. , Pavone L. , Musumeci S. : Thalamic syndrome in children with measles infection and selective, reversible thalamic involvement. Pediatrics 1998;101:112—119.

32.

Yagishita A. , Nakano I. , Ushioda T. , et al: Acute encephalopathy with bilateral thalamotegmental involvement in infants and children: Imaging and pathology findings. AJNR Am J Neuroradiol 1995;16:439—447.

33.

Nakai Y. , Itoh M. , Miziguchi M. , et al: Apoptosis and microglial activation in influenza encephalopathy . Acta Neuropathol (Berl) 2003; 105:233—239.