The interplay of infection and genetics in acute necrotizing encephalopathy

Current Opinion in Pediatrics

Volumn 22, Issue 6, 2010, Pages 751-757

  Neilson, Derek E ^a  

^a UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

Author keywords

acute; encephalopathy; influenza; necrotizing; RANBP2

Indexed keywords

IMMUNOGLOBULIN; INTERLEUKIN 6; NUCLEAR PROTEIN; RANBP2 PROTEIN; STEROID; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

CLINICAL FEATURE; COMPUTER ASSISTED TOMOGRAPHY; DIFFUSION COEFFICIENT; EARLY DIAGNOSIS; FLUID ATTENUATED INVERSION RECOVERY; GENETIC ASSOCIATION; GENETIC LINKAGE; HUMAN; IMMUNOPATHOLOGY; LEIGH DISEASE; MISSENSE MUTATION; NEUROIMAGING; NEUROPATHOLOGY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEAR PORE; OXIDATIVE STRESS; POINT MUTATION; PRIORITY JOURNAL; REVIEW; SEIZURE; UBIQUITINATION; VIRUS INFECTION;

HUMANS; INFLUENZA, HUMAN; LEUKOENCEPHALITIS, ACUTE HEMORRHAGIC; MOLECULAR CHAPERONES; NUCLEAR PORE COMPLEX PROTEINS;

EID: 78649514657     PISSN: 10408703     EISSN: None     Source Type: Journal    
DOI: 10.1097/MOP.0b013e3283402bfe     Document Type: Review

References (77)

1. Neilson DE, Adams MD, Orr CM, 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. This is the first article to demonstrate the genetic cause for ANE1 and provides evidence for further genetic loci.
2. Gilson C, McFarland R, Forsyth R. Autosomal dominant acute necrotising encephalopathy: A case report with possible disease-expression modification by coincidental homocysteinuria. Eur J Paediatr Neurol 2010; 169:1299-1302. A case with ANE1 (common RANBP2 mutation) and homocystinuria, which possibly affected the threshold for ANE evolution.
3. Mizuguchi M. Acute necrotizing encephalopathy of childhood: A novel form of acute encephalopathy prevalent in Japan and Taiwan. Brain Dev 1997; 19:81-92.
4. Neilson DE, Eiben RM, Waniewski S, et al. Autosomal dominant acute necrotizing encephalopathy. Neurology 2003; 61:226-230.
5. Mizuguchi M, Abe J, Mikkaichi K, et al. Acute necrotising encephalopathy of childhood: A new syndrome presenting with multifocal, symmetric brain lesions. J Neurol Neurosurg Psychiatry 1995; 58:555-561.
6. Mastroyianni SD, Gionnis D, Voudris K, et al. Acute necrotizing encephalopathy of childhood in non-Asian patients: Report of three cases and literature review. J Child Neurol 2006; 21:872-879.
7. Troedson C, Gill D, Dale RC. Emergence of acute necrotising encephalopathy in Australia. J Paediatr Child Health 2008; 44:599-601.
8. Weitkamp JH, Spring MD, Brogan T, et al. Influenza A virus-associated acute necrotizing encephalopathy in the United States. Pediatr Infect Dis J 2004; 23:259-263.
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. Okabe N, Yamashita K, Taniguchi K, Inouye S. Influenza surveillance system of Japan and acute encephalitis and encephalopathy in the influenza season. Pediatr Int 2000; 42:187-191.
11. Togashi T, Matsuzono Y, Narita M, Morishima T. Influenza-associated acute encephalopathy in Japanese children in 1994-2002. Virus Res 2004; 103:75-78.
12. Sugaya N. Influenza-associated encephalopathy in Japan: Pathogenesis and treatment. Pediatr Int 2000; 42:215-218.
13. Mizuguchi M, Yamanouchi H, Ichiyama T, Shiomi M. Acute encephalopathy associated with influenza and other viral infections. Acta Neurol Scand Suppl 2007; 186:45-56.
14. Mizuguchi M, Hayashi M, Nakano I, Kuwashima M, et al. Concentric structure of thalamic lesions in acute necrotizing encephalopathy. Neuroradiology 2002; 44:489-493.
15. Sener RN. Acute necrotizing encephalopathy. Eur Radiol 2005; 15:395-396.
16. Albayram S, Bilgi Z, Selcuk H, et al. Diffusion-weighted MR imaging findings of acute necrotizing encephalopathy. AJNR Am J Neuroradiol 2004; 25:792-797.
17. Okumura A, Mizuguchi M, Kidokoro H, et al. Outcome of acute necrotizing encephalopathy in relation to treatment with corticosteroids and gammaglobulin. Brain Dev 2009; 31:221-227. This is the only study on treatment outcomes using comparison groups. It demonstrated better outcomes with early steroid use. Prior studies without control groups cannot separate treatment effect from spontaneous resolution.
18. Loh NR, Appleton DB. Untreated recurrent acute necrotising encephalopathy associated with RANBP2 mutation, and normal outcome in a Caucasian boy. Eur J Pediatr 2010; 169:1299-1302. This reiterates that ANE1, though severe in appearance, can have a good outcome.
19. Sugaya N. Influenza-associated encephalopathy in Japan. Semin Pediatr Infect Dis 2002; 13:79-84.
20. Martin A, Reade EP. Acute necrotizing encephalopathy progressing to brain death in a pediatric patient with novel influenza A (H1N1) infection. Clin Infect Dis 2010; 50:e50-e52. This study describes ANE in the context of pandemic H1N1.
21. Ormitti F, Ventura E, Summa A, et al. Acute necrotizing encephalopathy in a child during the 2009 influenza A(H1N1) pandemia: MR imaging in diagnosis and follow-up. AJNR Am J Neuroradiol 2010; 31:396-400. This study describes ANE in the context of pandemic H1N1.
22. Lyon JB, Remigio C, Milligan T, Deline C. Acute necrotizing encephalopathy in a child with H1N1 influenza infection. Pediatr Radiol 2010; 40:200-205. This study describes ANE in the context of pandemic H1N1.
23. Mariotti P, Iorio R, Frisullo G, et al. Acute necrotizing encephalopathy during novel influenza A (H1N1) virus infection. Ann Neurol 2010; 68:111-114. This study describes ANE in the context of pandemic H1N1.
24. Sazgar M, Robinson JL, Chan AK, Sinclair DB. Influenza B acute necrotizing encephalopathy: A case report and literature review. Pediatr Neurol 2003; 28:396-399.
25. Huang SM, Chen CC, Chiu PC, et al. Acute necrotizing encephalopathy of childhood associated with influenza type B virus infection in a 3-year-old girl. J Child Neurol 2004; 19:64-67.
26. Mastroyianni SD, Voudris KA, Katsarou E, et al. Acute necrotizing encephalopathy associated with parainfluenza virus in a Caucasian child. J Child Neurol 2003; 18:570-572.
27. Tran TD, Kubota M, Takeshita K, et al. Varicella-associated acute necrotizing encephalopathy with a good prognosis. Brain Dev 2001; 23:54-57.
28. Skelton BW, Hollingshead MC, Sledd AT, et al. Acute necrotizing encephalopathy of childhood: Typical findings in an atypical disease. Pediatr Radiol 2008; 38:810-813.
29. Oki J, Yoshida H, Tokumitsu A, et al. Serial neuroimages of acute necrotizing encephalopathy associated with human herpesvirus 6 infection. Brain Dev 1995; 17:356-359.
30. Ohsaka M, Houkin K, Takigami M, Koyanagi I. Acute necrotizing encephalopathy associated with human herpesvirus-6 infection. Pediatr Neurol 2006; 34:160-163.
31. Narita M. Acute necrotizing encephalopathy by Mycoplasma pneumoniae infection? Arch Intern Med 2002; 162:1647.
32. Ashtekar CS, Jaspan T, Thomas D, et al. Acute bilateral thalamic necrosis in a child with Mycoplasma pneumoniae. Dev Med Child Neurol 2003; 45:634-637.
33. Aydin H, Ozgul E, Agildere AM. Acute necrotizing encephalopathy secondary to diphtheria, tetanus toxoid and whole-cell pertussis vaccination: Diffusionweighted imaging and proton MR spectroscopy findings. Pediatr Radiol 2010; 40:1281-1284. The mechanism of vaccine-induced ANE has not been previously reported.
34. Nakai Y, Itoh M, Mizuguchi M, et al. Apoptosis and microglial activation in influenza encephalopathy. Acta Neuropathol 2003; 105:233-239.
35. Wang GF, Li W, Li K. Acute encephalopathy and encephalitis caused by influenza virus infection. Curr Opin Neurol 2010; 23:305-311. An up-to-date review on influenza-related encephalopathy.
36. Okumura A, Abe S, Kidokoro H, Mizuguchi M. Acute necrotizing encephalopathy: A comparison between influenza and noninfluenza cases. Microbiol Immunol 2009; 53:277-280. In a 'guilt-by-association' interpretation, ANE has been regarded as a subset of IAE. The absence of differences between influenza-based and noninfluenza-based ANE affirms that the host, not the virus, is the most important factor.
37. Ng WF, Chiu SC, Lam DS, et al. A 7-year-old boy dying of acute encephalopathy. Brain Pathol 2010; 20:261-264. This unusual case appears similar to ANE, but revealed the additional finding of an exudative vasculopathy. Evidence suggested two closely spaced influenza infections that preceded and precipitated the ANE.
38. Ichiyama T, Endo S, Kaneko M, et al. Serum cytokine concentrations of influenza-associated acute necrotizing encephalopathy. Pediatr Int 2003; 45:734-736.
39. Aiba H, Mochizuki M, Kimura M, et al. Predictive value of serum interleukin-6 level in influenza virus-associated encephalopathy. Neurology 2001; 57:295-299.
40. Ichiyama T, Isumi H, Ozawa H, et al. Cerebrospinal fluid and serum levels of cytokines and soluble tumor necrosis factor receptor in influenza virusassociated encephalopathy. Scand J Infect Dis 2003; 35:59-61.
41. Hosoya M, Nunoi H, Aoyama M, et al. Cytochrome c and tumor necrosis factor-alpha values in serum and cerebrospinal fluid of patients with influenzaassociated encephalopathy. Pediatr Infect Dis J 2005; 24:467-470.
42. Gijbels K, Van Damme J, Proost P, et al. Interleukin 6 production in the central nervous system during experimental autoimmune encephalomyelitis. Eur J Immunol 1990; 20:233-235.
43. Frei K, Malipiero UV, Leist TP, et al. On the cellular source and function of interleukin 6 produced in the central nervous system in viral diseases. Eur J Immunol 1989; 19:689-694.
44. O'Callaghan JP, Sriram K, Miller DB. Defining 'neuroinflammation'. Ann N Y Acad Sci 2008; 1139:318-330.
45. Brett FM, Mizisin AP, Powell HC, Campbell IL. Evolution of neuropathologic abnormalities associated with blood-brain barrier breakdown in transgenic mice expressing interleukin-6 in astrocytes. J Neuropathol Exp Neurol 1995; 54:766-775.
46. Penkowa M, Giralt M, Lago N, et al. Astrocyte-targeted expression of IL-6 protects theCNS against a focal brain injury. Exp Neurol 2003; 181:130-148.
47. Marco EJ, Anderson JE, Neilson DE, Strober JB. Acute necrotizing encephalopathy in 3 brothers. Pediatrics 2010; 125:e693-e698. Three affected brothers in a consanguineous family provide evidence for an autosomal recessive locus and reveals another link to mitochondrial involvement through 'ragged red fibers' on muscle biopsy.
48. Wu J, Matunis MJ, Kraemer D, et al. Nup358, a cytoplasmically exposed nucleoporin with peptide repeats, Ran-GTP binding sites, zinc fingers, a cyclophilin A homologous domain, and a leucine-rich region. J Biol Chem 1995; 270:14209-14213.
49. Yokoyama N, Hayashi N, Seki T, et al. A giant nucleopore protein that binds Ran/TC4. Nature 1995; 376:184-188.
50. Cook A, Bono F, Jinek M, Conti E. Structural biology of nucleocytoplasmic transport. Annu Rev Biochem 2007; 76:647-671.
51. Singh BB, Patel HH, Roepman R, et al. The zinc finger cluster domain of RanBP2 is a specific docking site for the nuclear export factor, exportin-1. J Biol Chem 1999; 274:37370-37378.
52. Kuersten S, Arts GJ, Walther TC, et al. Steady-state nuclear localization of exportin-t involves RanGTP binding and two distinct nuclear pore complex interaction domains. Mol Cell Biol 2002; 22:5708-5720.
53. Saitoh H, Sparrow DB, Shiomi T, et al. Ubc9p and the conjugation of SUMO-1 to RanGAP1 and RanBP2. Curr Biol 1998; 8:121-124.
54. Joseph J, Tan SH, Karpova TS, et al. SUMO-1 targets RanGAP1 to kinetochores and mitotic spindles. J Cell Biol 2002; 156:595-602.
55. Kirsh O, Seeler JS, Pichler A, et al. The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase. EMBO J 2002; 21:2682-2691.
56. Pichler A, Gast A, Seeler JS, et al. The nucleoporin RanBP2 has SUMO1 E3 ligase activity. Cell 2002; 108:109-120.
57. Saitoh H, Pizzi MD, Wang J. Perturbation of SUMOlation enzyme Ubc9 by distinct domain within nucleoporin RanBP2/Nup358. J Biol Chem 2002; 277:4755-4763.
58. Saitoh N, Uchimura Y, Tachibana T, et al. In situ SUMOylation analysis reveals a modulatory role of RanBP2 in the nuclear rim and PML bodies. Exp Cell Res 2006; 312:1418-1430.
59. Klein UR, Haindl M, Nigg EA, Muller S. RanBP2 and SENP3 function in a mitotic SUMO2/3 conjugation-deconjugation cycle on Borealin. Mol Biol Cell 2009; 20:410-418.
60. Salina D, Enarson P, Rattner JB, Burke B. Nup358 integrates nuclear envelope breakdown with kinetochore assembly. J Cell Biol 2003; 162: 991-1001.
61. Prunuske AJ, Liu J, Elgort S, et al. Nuclear envelope breakdown is coordinated by both Nup358/RanBP2 and Nup153, two nucleoporins with zinc finger modules. Mol Biol Cell 2006; 17:760-769.
62. Joseph J, Dasso M. The nucleoporin Nup358 associates with and regulates interphase microtubules. FEBS Lett 2008; 582:190-196.
63. Murawala P, Tripathi MM, Vyas P, et al. Nup358 interacts with APC and plays a role in cell polarization. J Cell Sci 2009; 122 (Pt 17):3113-3122.
64. Joseph J, Liu ST, Jablonski SA, et al. The RanGAP1-RanBP2 complex is essential for microtubule-kinetochore interactions in vivo. Curr Biol 2004; 14:611-617.
65. Rundle NT, Nelson J, Flory MR, et al. An ent-kaurene that inhibits mitotic chromosome movement and binds the kinetochore protein ran-binding protein 2. ACS Chem Biol 2006; 1:443-450.
66. Torosantucci L, De Luca M, Guarguaglini G, et al. Localized RanGTP accumulation promotes microtubule nucleation at kinetochores in somatic mammalian cells. Mol Biol Cell 2008; 19:1873-1882.
67. Cai Y, Singh BB, Aslanukov A, et al. The docking of kinesins, KIF5B and KIF5C, to Ran-binding protein 2 (RanBP2) is mediated via a novel RanBP2 domain. J Biol Chem 2001; 276:41594-41602.
68. Mavlyutov TA, Cai Y, Ferreira PA. Identification of RanBP2- and kinesinmediated transport pathways with restricted neuronal and subcellular localization. Traffic 2002; 3:630-640.
69. Cho KI, Cai Y, Yi H, et al. Association of the kinesin-binding domain of RanBP2 to KIF5B and KIF5C determines mitochondria localization and function. Traffic 2007; 8:1722-1735.
70. Cho KI, Yi H, Desai R, et al. RANBP2 is an allosteric activator of the conventional kinesin-1 motor protein, KIF5B, in a minimal cell-free system. EMBO Rep 2009; 10:480-486. The nonnuclear effects of RANBP2 continue to be expanded.
71. Aslanukov A, Bhowmick R, Guruju M, et al. RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism. PLoS Genet 2006; 2:e177.
72. Cho KI, Yi H, Yeh A, et al. Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons. Cell Death Differ 2009; 16:287-297. This study provides an interesting correlation between free radicals, free fatty acids, and retinal degeneration in the context of RANBP2 haploinsufficiency.
73. Dawlaty MM, Malureanu L, Jeganathan KB, et al. Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha. Cell 2008; 133:103-115.
74. Um JW, Min DS, Rhim H, et al. Parkin ubiquitinates and promotes the degradation of RanBP2. J Biol Chem 2006; 281:3595-3603.
75. Yao D, Kuwajima M, Chen Y, et al. Impaired long-chain fatty acid metabolism in mitochondria causes brain vascular invasion by a nonneurotropic epidemic influenza A virus in the newborn/suckling period: Implications for influenzaassociated encephalopathy. Mol Cell Biochem 2007; 299:85-92.
76. Yao D, Mizuguchi H, Yamaguchi M, et al. Thermal instability of compound variants of carnitine palmitoyltransferase II and impaired mitochondrial fuel utilization in influenza-associated encephalopathy. Hum Mutat 2008; 29:718-727.
77. Chen Y, Mizuguchi H, Yao D, et al. Thermolabile phenotype of carnitine palmitoyltransferase II variations as a predisposing factor for influenza-associated encephalopathy. FEBS Lett 2005; 579:2040-2044.