Journal of Neurology

, 256:2052 | Cite as

An evaluation of the usefulness of neuroimaging for the diagnosis of Japanese encephalitis

  • N. M. Dung
  • Lance Turtle
  • W. K. Chong
  • N. T. Mai
  • T. T. Thao
  • T. T. Thuy
  • R. Kneen
  • N. H. Phu
  • B. Wills
  • J. Farrar
  • K. Das
  • Tom SolomonEmail author
Original Communication


Japanese encephalitis virus (JEV) is estimated to cause 30–50,000 cases of encephalitis every year. The disease occurs mainly in rural Asia and is transmitted to humans from birds and pigs by mosquitoes of the genus Culex. JE is diagnosed with antibody testing of the serum and CSF, but this is not available in many hospitals. Neuroimaging abnormalities, particularly thalamic hypodensity on computed tomography (CT) and hyperintensity on T2 weighted magnetic resonance imaging (MRI) have been described in case studies, but their usefulness for diagnosing JE is not known. We have therefore evaluated the usefulness of neuroimaging (CT and MRI) for the diagnosis of JE. The findings of thalamic lesions were compared with the final serological diagnosis in a cohort of 75 patients (children and adults) with suspected CNS infections in Southern Vietnam, a JEV endemic area. Thalamic lesions on CT and/or MRI combined had sensitivity 23% (95% confidence interval 12.9–33.1%), specificity 100%, positive predictive value 100% and negative predictive value 42.1% (95% confidence interval 30.2–53.8%) for a diagnosis of JE in this cohort. Over time, the thalamic lesions resolved in some patients. One patient showed disappearance of lesions on CT followed by reappearance of the lesions some time later, known as the fogging effect. In this setting, the presence of thalamic abnormalities suggested the diagnosis of JE, but their absence did not exclude it.


Japanese encephalitis Neuroimaging Diagnosis Computed tomography (CT) Magnetic resonance imaging (MRI) Serology 



We are grateful to the director and staff of the Centre for Tropical Diseases for their support, in particular Tran Tinh Hien and the doctors and nurses of the adult and paediatric intensive care units. David Vaughn and staff at AFRIMS, Bangkok gave diagnostic support, and Mani Putharan at the Walton Centre gave assistance with the images in this paper. This work was funded by the Wellcome Trust of Great Britain. TS is an MRC Senior Clinical Fellow.


  1. 1.
    World Health Organisation (2006) Japanese encephalitis vaccines. Wkly Epidemiol Rec 81(34/35):331–340Google Scholar
  2. 2.
    Becker H, Desch H, Hacker H, Pencz A (1979) CT fogging effect with ischemic cerebral infarcts. Neuroradiology 18:185–192. doi: 10.1007/BF00345723 CrossRefPubMedGoogle Scholar
  3. 3.
    Bosanko CM, Gilroy J, Wang AM, Sanders W, Dulai M, Wilson J, Blum K (2003) West Nile virus encephalitis involving the substantia nigra: neuroimaging and pathologic findings with literature review. Arch Neurol 60:1448–1452. doi: 10.1001/archneur.60.10.1448 CrossRefPubMedGoogle Scholar
  4. 4.
    Burke DS, Nisalak A, Ussery MA (1982) Antibody capture immunoassay detection of Japanese encephalitis virus immunoglobulin m and g antibodies in cerebrospinal fluid. J Clin Microbiol 16:1034–1042PubMedGoogle Scholar
  5. 5.
    Burke DS, Nisalak A, Ussery MA, Laorakpongse T, Chantavibul S (1985) Kinetics of IgM and IgG responses to Japanese encephalitis virus in human serum and cerebrospinal fluid. J Infect Dis 151:1093–1099PubMedGoogle Scholar
  6. 6.
    Deresiewicz RL, Thaler SJ, Hsu L, Zamani AA (1997) Clinical and neuroradiographic manifestations of eastern equine encephalitis. N Engl J Med 336:1867–1874. doi: 10.1056/NEJM199706263362604 CrossRefPubMedGoogle Scholar
  7. 7.
    Desai A, Shankar SK, Ravi V, Chandramuki A, Gourie-Devi M (1995) Japanese encephalitis virus antigen in the human brain and its topographic distribution. Acta Neuropathol 89:368–373. doi: 10.1007/BF00309631 CrossRefPubMedGoogle Scholar
  8. 8.
    Edgren DC, Palladino VS, Arnold A (1958) Japanese B and mumps encephalitis: a clinicopathological report of simultaneous outbreaks on the island of Guam. Am J Trop Med Hyg 7:471–480PubMedGoogle Scholar
  9. 9.
    Einsiedel L, Kat E, Ravindran J, Slavotinek J, Gordon DL (2003) MR findings in Murray Valley encephalitis. AJNR Am J Neuroradiol 24:1379–1382PubMedGoogle Scholar
  10. 10.
    German AC, Myint KS, Mai NT, Pomeroy I, Phu NH, Tzartos J, Winter P, Collett J, Farrar J, Barrett A, Kipar A, Esiri MM, Solomon T (2006) A preliminary neuropathological study of Japanese encephalitis in humans and a mouse model. Trans R Soc Trop Med Hyg 100:1135–1145. doi: 10.1016/j.trstmh.2006.02.008 CrossRefPubMedGoogle Scholar
  11. 11.
    Handique SK, Das RR, Barman K, Medhi N, Saharia B, Saikia P, Ahmed SA (2006) Temporal lobe involvement in Japanese encephalitis: problems in differential diagnosis. AJNR Am J Neuroradiol 27:1027–1031PubMedGoogle Scholar
  12. 12.
    Innis BL, Nisalak A, Nimmannitya S, Kusalerdchariya S, Chongswasdi V, Suntayakorn S, Puttisri P, Hoke CH (1989) An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate. Am J Trop Med Hyg 40:418–427PubMedGoogle Scholar
  13. 13.
    Johnson RT, Burke DS, Elwell M, Leake CJ, Nisalak A, Hoke CH, Lorsomrudee W (1985) Japanese encephalitis: immunocytochemical studies of viral antigen and inflammatory cells in fatal cases. Ann Neurol 18:567–573. doi: 10.1002/ana.410180510 CrossRefPubMedGoogle Scholar
  14. 14.
    Kalita J, Misra UK (2000) Comparison of CT scan and MRI findings in the diagnosis of Japanese encephalitis. J Neurol Sci 174:3–8. doi: 10.1016/S0022-510X(99)00318-4 CrossRefPubMedGoogle Scholar
  15. 15.
    Kalita J, Misra UK, Pandey S, Dhole TN (2003) A comparison of clinical and radiological findings in adults and children with Japanese encephalitis. Arch Neurol 60:1760–1764. doi: 10.1001/archneur.60.12.1760 CrossRefPubMedGoogle Scholar
  16. 16.
    Kamble R, Peruvamba JN, Kovoor J, Ravishankar S, Kolar BS (2007) Bilateral thalamic involvement in dengue infection. Neurol India 55:418–419. doi: 10.4103/0028-3886.37103 CrossRefPubMedGoogle Scholar
  17. 17.
    Kimura K, Dosaka A, Hashimoto Y, Yasunaga T, Uchino M, Ando M (1997) Single-photon emission CT findings in acute Japanese encephalitis. AJNR Am J Neuroradiol 18:465–469PubMedGoogle Scholar
  18. 18.
    Kumar S, Misra UK, Kalita J, Salwani V, Gupta RK, Gujral R (1997) MRI in Japanese encephalitis. Neuroradiology 39:180–184. doi: 10.1007/s002340050388 CrossRefPubMedGoogle Scholar
  19. 19.
    Lorenzl S, Pfister HW, Padovan C, Yousry T (1996) MRI abnormalities in tick-borne encephalitis. Lancet 347:698–699. doi: 10.1016/S0140-6736(96)91256-8 CrossRefPubMedGoogle Scholar
  20. 20.
    Marjelund S, Tikkakoski T, Tuisku S, Raisanen S (2004) Magnetic resonance imaging findings and outcome in severe tick-borne encephalitis. Report of four cases and review of the literature. Acta Radiol 45:88–94. doi: 10.1080/02841850410003356 CrossRefPubMedGoogle Scholar
  21. 21.
    Misra UK, Kalita J (1997) Movement disorders in Japanese encephalitis. J Neurol 244:299–303. doi: 10.1007/s004150050090 CrossRefPubMedGoogle Scholar
  22. 22.
    Misra UK, Kalita J (2001) Seizures in Japanese encephalitis. J Neurol Sci 190:57–60. doi: 10.1016/S0022-510X(01)00589-5 CrossRefPubMedGoogle Scholar
  23. 23.
    Misra UK, Kalita J, Goel D, Mathur A (2003) Clinical, radiological and neurophysiological spectrum of JEV encephalitis and other non-specific encephalitis during post-monsoon period in India. Neurol India 51:55–59PubMedGoogle Scholar
  24. 24.
    Misra UK, Kalita J, Jain SK, Mathur A (1994) Radiological and neurophysiological changes in Japanese encephalitis. J Neurol Neurosurg Psychiatry 57:1484–1487. doi: 10.1136/jnnp.57.12.1484 CrossRefPubMedGoogle Scholar
  25. 25.
    Miyake M (1964) The pathology of Japanese encephalitis. A review. Bull World Health Organ 30:153–160PubMedGoogle Scholar
  26. 26.
    Molyneux ME, Taylor TE, Wirima JJ, Borgstein A (1989) Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med 71:441–459PubMedGoogle Scholar
  27. 27.
    Nakashima A, Horichi Y, Takagi Y, Miyamoto S, Takashima S, Inoue H (1999) A case of Japanese encephalitis: CT and MRI findings in acute and convalescent stages. Radiat Med 17:369–371PubMedGoogle Scholar
  28. 28.
    Ooi MH, Lewthwaite P, Lai BF, Mohan A, Clear D, Lim L, Krishnan S, Preston T, Chieng CH, Tio PH, Wong SC, Cardosa J, Solomon T (2008) The epidemiology, clinical features, and long-term prognosis of Japanese encephalitis in Central Sarawak, Malaysia, 1997–2005. Clin Infect Dis 47(4):458–468CrossRefPubMedGoogle Scholar
  29. 29.
    Pradhan S, Pandey N, Shashank S, Gupta RK, Mathur A (1999) Parkinsonism due to predominant involvement of substantia nigra in Japanese encephalitis. Neurology 53:1781–1786PubMedGoogle Scholar
  30. 30.
    Sejvar JJ, Haddad MB, Tierney BC, Campbell GL, Marfin AA, Van Gerpen JA, Fleischauer A, Leis AA, Stokic DS, Petersen LR (2003) Neurologic manifestations and outcome of West Nile virus infection. JAMA 290:511–515. doi: 10.1001/jama.290.4.511 CrossRefPubMedGoogle Scholar
  31. 31.
    Shoji H, Hiraki Y, Kuwasaki N, Toyomasu T, Kaji M, Okudera T (1989) Japanese encephalitis in the Kurume region of Japan: CT and MRI findings. J Neurol 236:255–259. doi: 10.1007/BF00314452 CrossRefPubMedGoogle Scholar
  32. 32.
    Shoji H, Kida H, Hino H, Matsuura S, Kojima K, Abe T, Utsunomiya H, Okada Y, Nakamura Y, Okudera T (1994) Magnetic resonance imaging findings in Japanese encephalitis. White matter lesions. J Neuroimaging 4:206–211PubMedGoogle Scholar
  33. 33.
    Shoji H, Murakami T, Murai I, Kida H, Sato Y, Kojima K, Abe T, Okudera T (1990) A follow-up study by CT and MRI in 3 cases of Japanese encephalitis. Neuroradiology 32:215–219. doi: 10.1007/BF00589115 CrossRefPubMedGoogle Scholar
  34. 34.
    Skriver EB, Olsen TS (1981) Transient disappearance of cerebral infarcts on CT scan, the so-called fogging effect. Neuroradiology 22:61–65. doi: 10.1007/BF00344775 CrossRefPubMedGoogle Scholar
  35. 35.
    Solomon T, Dung NM, Kneen R, le Thao TT, Gainsborough M, Nisalak A, Day NP, Kirkham FJ, Vaughn DW, Smith S, White NJ (2002) Seizures and raised intracranial pressure in Vietnamese patients with Japanese encephalitis. Brain 125:1084–1093. doi: 10.1093/brain/awf116 CrossRefPubMedGoogle Scholar
  36. 36.
    Solomon T, Dung NM, Vaughn DW, Kneen R, Thao LT, Raengsakulrach B, Loan HT, Day NP, Farrar J, Myint KS, Warrell MJ, James WS, Nisalak A, White NJ (2000) Neurological manifestations of dengue infection. Lancet 355:1053–1059. doi: 10.1016/S0140-6736(00)02036-5 CrossRefPubMedGoogle Scholar
  37. 37.
    Solomon T, Dung NM, Wills B, Kneen R, Gainsborough M, Diet TV, Thuy TT, Loan HT, Khanh VC, Vaughn DW, White NJ, Farrar JJ (2003) Interferon alfa-2a in Japanese encephalitis: a randomised double-blind placebo-controlled trial. Lancet 361:821–826. doi: 10.1016/S0140-6736(03)12709-2 CrossRefPubMedGoogle Scholar
  38. 38.
    Solomon T, Fisher AF, Beasley DW, Mandava P, Granwehr BP, Langsjoen H, Travassos Da Rosa AP, Barrett AD, Tesh RB (2003) Natural and nosocomial infection in a patient with West Nile encephalitis and extrapyramidal movement disorders. Clin Infect Dis 36:E140–E145. doi: 10.1086/374936 CrossRefPubMedGoogle Scholar
  39. 39.
    Solomon T, Kneen R, Dung NM, Khanh VC, Thuy TT, Ha DQ, Day NP, Nisalak A, Vaughn DW, White NJ (1998) Poliomyelitis-like illness due to Japanese encephalitis virus. Lancet 351:1094–1097. doi: 10.1016/S0140-6736(97)07509-0 CrossRefPubMedGoogle Scholar
  40. 40.
    Solomon T, Thao LT, Dung NM, Kneen R, Hung NT, Nisalak A, Vaughn DW, Farrar J, Hien TT, White NJ, Cardosa MJ (1998) Rapid diagnosis of Japanese encephalitis by using an immunoglobulin M dot enzyme immunoassay. J Clin Microbiol 36:2030–2034PubMedGoogle Scholar
  41. 41.
    Teasdale G, Jennett B (1974) Assessment of coma and impaired consciousness. A practical scale. Lancet 2:81–84. doi: 10.1016/S0140-6736(74)91639-0 CrossRefPubMedGoogle Scholar
  42. 42.
    Toyomasu T, Nakashima K, Matsumoto T, Shida K (1982) CT findings in a case of Japanese encephalitis. Clin Neurol (Tokyo) 22:891–895Google Scholar
  43. 43.
    Verity CM, Butler NR, Golding J (1985) Febrile convulsions in a national cohort followed up from birth. I–Prevalence and recurrence in the first five years of life. Br Med J (Clin Res Ed) 290:1307–1310CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • N. M. Dung
    • 1
  • Lance Turtle
    • 2
    • 3
  • W. K. Chong
    • 4
  • N. T. Mai
    • 1
  • T. T. Thao
    • 1
  • T. T. Thuy
    • 1
  • R. Kneen
    • 5
  • N. H. Phu
    • 1
  • B. Wills
    • 6
  • J. Farrar
    • 6
  • K. Das
    • 7
  • Tom Solomon
    • 3
    • 7
    Email author
  1. 1.Centre for Tropical Diseases, Cho Quan HospitalHo Chi Minh CityVietnam
  2. 2.Royal Liverpool University HospitalLiverpoolUK
  3. 3.Brain Infections Group, Divisions of Neurological Science and Medical MicrobiologyUniversity of LiverpoolLiverpoolUK
  4. 4.Great Ormond Street Hospital for Children NHS TrustLondonUK
  5. 5.Royal Liverpool Children’s NHS TrustLiverpoolUK
  6. 6.Oxford University Wellcome Trust Clinical Research Unit, Centre for Tropical DiseasesHo Chi Minh CityVietnam
  7. 7.Walton Centre for Neurology and Neurosurgery NHS TrustLiverpoolUK

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