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Neuropediatrics 2002; 33(5): 266-270
DOI: 10.1055/s-2002-36739
Short Communication

Georg Thieme Verlag Stuttgart · New York

A Case of Diffuse Leptomeningeal Oligodendrogliomatosis Associated with HHV-6 Variant A

T. Stödberg 1 , Y. Deniz 2 , N. Esteitie 1 , B. Jacobsson 3 , M. Mousavi-Jazi 4 , H. Dahl 4 , B. Zweygberg Wirgart 5 , L. Grillner 5 , A. Linde 4
  • 1Department of Neuropediatrics, Astrid Lindgren Children's Hospital, Karolinska Hospital, Stockholm, Sweden
  • 2Department of Allergy, Asthma and Immunology, Astrid Lindgren Children's Hospital, Karolinska Hospital, Stockholm, Sweden
  • 3Department of Pathology, Karolinska Hospital, Stockholm, Sweden
  • 4Swedish Institute for Infectious Disease Control, Microbiology and Tumourbiology Centre, Karolinska Institute, Stockholm, Sweden
  • 5Department of Clinical Microbiology, Karolinska Hospital, Stockholm, Sweden
Further Information

Publication History

Received: 2 January 2002

Accepted after Revision: 12 June 2002

Publication Date:
21 January 2003 (online)

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Abstract

We describe a rare case of diffuse leptomeningeal oligodendrogliomatosis associated with the human herpes virus 6 variant A (HHV-6 A). A 2-year-old boy presented with progressive neurological symptoms and hydrocephalus. The patient had a VP shunt placement but did not fully recover. HHV-6 A was detected in both CSF and serum by nested PCR. His symptoms improved repeatedly, but temporarily, on antiviral treatment. An open brain biopsy, ten months after presentation, revealed leptomeningeal tumour as well as the presence of viral DNA in the tumour tissue. The role of HHV-6 A could be that of a reactivated opportunist. However, this case also raises the question whether this neurotropic virus, with malignant transforming properties in vitro, may have a role in pathogenesis in some cases of brain malignancy.

Key words

Human Herpes Virus 6 - PCR - CNS Disease - Hydrocephalus - Neoplasms - Oligodendroglioma

References

  • 1 Ahtiluoto S, Mannonen L, Paetau A, Vaheri A, Koskiniemi M, Rautiainen P. et al . In situ hybridization detection of human herpes virus 6 in brain tissue from fatal encephalitis.  Pediatrics. 2000;  105 431-433
    CrossrefPubMedSearch in Google Scholar
  • 2 Albright A V, Lavi E, Black J B, Goldberg S, O'Connor M J, Gonzalez-Scarano F. The effect of human herpes virus-6 (HHV-6) on cultured human neural cells: oligodendrocytes and microglia.  J Neurovirol. 1998;  4 486-494
    PubMedSearch in Google Scholar
  • 3 Ambinder R F, Lemas M V, Moore S, Yang J, Fabian D, Krone C. Epstein-Barr virus and lymphoma.  Cancer Treat Res. 1999;  99 27-45
    PubMedSearch in Google Scholar
  • 4 Armao D M, Stone J, Castillo M, Mitchell K M, Bouldin T W, Suzuki K. Diffuse leptomeningeal oligodendrogliomatosis: radiologic/pathologic correlation.  AJNR Am J Neuroradiol. 2000;  21 1122-1126
    PubMedSearch in Google Scholar
  • 5 Asano Y, Yoshikawa T, Kajita Y, Ogura R, Suga S, Yazaki T. et al . Fatal encephalitis/encephalopathy in primary human herpes virus-6 infection.  Arch Dis Child. 1992;  67 1484-1485
    PubMedSearch in Google Scholar
  • 6 Blumberg B M, Mock D J, Powers J M, Ito M, Assouline J G, Baker J V. et al . The HHV6 paradox: ubiquitous commensal or insidious pathogen? A two-step in situ PCR approach.  J Clin Virol. 2000;  16 159-178
    PubMedSearch in Google Scholar
  • 7 Braun D K, Dominguez G, Pellett P E. Human herpes virus 6.  Clin Microbiol Rev. 1997;  10 521-567
    PubMedSearch in Google Scholar
  • 8 Challoner P B, Smith K T, Parker J D, MacLeod D L, Coulter S N, Rose T M. et al . Plaque-associated expression of human herpes virus 6 in multiple sclerosis.  Proc Natl Acad Sci USA. 1995;  92 7440-7444
    PubMedSearch in Google Scholar
  • 9 Chan P K, Ng H K, Cheng A F. Detection of human herpes viruses 6 and 7 genomic sequences in brain tumours.  J Clin Pathol. 1999;  52 620-623
    PubMedSearch in Google Scholar
  • 10 Chan P K, Ng H K, Hui M, Cheng A F. Prevalence and distribution of human herpes virus 6 variants A and B in adult human brain.  J Med Virol. 2001;  64 42-46
    CrossrefPubMedSearch in Google Scholar
  • 11 Cooper I S, Kernohan J W. Heterotopic glial nests in the subarachnoid space: histopathologic characteristics, mode of origin and relation to meningeal gliomas.  J Neuropathol Exp Neurol. 2001;  10 16-29
    PubMedSearch in Google Scholar
  • 12 Cuomo L, Trivedi P, Cardillo M R, Gagliardi F M, Vecchione A, Caruso R. et al . Human herpes virus 6 infection in neoplastic and normal brain tissue.  J Med Virol. 2001;  63 45-51
    CrossrefPubMedSearch in Google Scholar
  • 13 Di Luca D, Dolcetti R, Mirandola P, Secchiero P, Carbone A. et al . Human herpes virus 6: a survey of presence and variant distribution in normal peripheral lymphocytes and lymphoproliferative disorders.  J Infect Dis. 1994;  170 211-215
    PubMedSearch in Google Scholar
  • 14 Drobyski W R, Knox K K, Majewski D, Carrigan D R. Brief report: fatal encephalitis due to variant B human herpes virus-6 infection in a bone marrow-transplant recipient.  N Engl J Med. 1994;  330 1356-1360
    CrossrefPubMedSearch in Google Scholar
  • 15 Enbom M, Strand A, Falk K I, Linde A. Detection of Epstein-Barr virus, but not human herpes virus 8, DNA in cervical secretions from Swedish women by real-time polymerase chain reaction.  Sex Transm Dis. 2001;  28 300-306
    PubMedSearch in Google Scholar
  • 16 Furukawa M, Yasukawa M, Yakushijin Y, Fujita S. Distinct effects of human herpes virus 6 and human herpes virus 7 on surface molecule expression and function of CD4 + T cells.  J Immunol. 1994;  152 5768-5775
    PubMedSearch in Google Scholar
  • 17 Gaines H, Andersson L, Biberfeld G. A new method for measuring lymphoproliferation at the single-cell level in whole blood cultures by flow cytometry.  J Immunol Methods. 1996;  195 63-72
    CrossrefPubMedSearch in Google Scholar
  • 18 Gao S J, Kingsley L, Hoover D R, Spira T J, Rinaldo C R, Saah A. et al . Seroconversion to antibodies against Kaposi's sarcoma-associated herpes virus-related latent nuclear antigens before the development of Kaposi's sarcoma.  N Engl J Med. 1996;  335 233-241
    CrossrefPubMedSearch in Google Scholar
  • 19 Hall C B, Caserta M T, Schnabel K C, Long C, Epstein L G, Insel R A. et al . Persistence of human herpes virus 6 according to site and variant: possible greater neurotropism of variant A.  Clin Infect Dis. 1998;  26 132-137
    CrossrefPubMedSearch in Google Scholar
  • 20 Hall C B, Long C E, Schnabel K C, Caserta M T, McIntyre K M, Costanzo M A. et al . Human herpes virus-6 infection in children. A prospective study of complications and reactivation.  N Engl J Med. 1994;  331 432-438
    CrossrefPubMedSearch in Google Scholar
  • 21 He J, McCarthy M, Zhou Y, Chandran B, Wood C. Infection of primary human fetal astrocytes by human herpes virus 6.  J Virol. 1996;  70 1296-1300
    PubMedSearch in Google Scholar
  • 22 Huang Y Q, Li J J, Kaplan M H, Poiesz B, Katabira E, Zhang W C. et al . Human herpes virus-like nucleic acid in various forms of Kaposi's sarcoma.  Lancet. 1995;  345 759-761
    CrossrefPubMedSearch in Google Scholar
  • 23 Kashanchi F, Araujo J, Doniger J, Muralidhar S, Hoch R, Khleif S. et al . Human herpes virus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant transforming activity and its protein binds to p53.  Oncogene. 1997;  14 359-367
    CrossrefPubMedSearch in Google Scholar
  • 24 Knox K K, Harrington D P, Carrigan D R. Fulminant human herpes virus six encephalitis in a human immunodeficiency virus-infected infant.  J Med Virol. 1995;  45 288-292
    PubMedSearch in Google Scholar
  • 25 Krueger G R, Koch B, Ramon A, Ablashi D V, Salahuddin S Z, Josephs S F. et al . Antibody prevalence to HBLV (human herpes virus-6, HHV-6) and suggestive pathogenicity in the general population and in patients with immune deficiency syndromes.  J Virol Methods. 1988;  21 125-131
    CrossrefPubMedSearch in Google Scholar
  • 26 Linde A, Dahl H, Wahren B, Fridell E, Salahuddin Z, Biberfeld P. IgG antibodies to human herpes virus-6 in children and adults and in primary Epstein-Barr virus infections and cytomegalovirus infections [corrected].  J Virol Methods. 1988;  21 117-123
    CrossrefPubMedSearch in Google Scholar
  • 27 Luppi M, Barozzi P, Maiorana A, Marasca R, Trovato R, Fano R. et al . Human herpes virus-6: a survey of presence and distribution of genomic sequences in normal brain and neuroglial tumors.  J Med Virol. 1995;  47 105-111
    PubMedSearch in Google Scholar
  • 28 McCullers J A, Lakeman F D, Whitley R J. Human herpes virus 6 is associated with focal encephalitis.  Clin Infect Dis. 1995;  21 571-576
    PubMedSearch in Google Scholar
  • 29 Ng H K, Poon W S. Diffuse leptomeningeal gliomatosis with oligodendroglioma.  Pathology. 1999;  31 59-63
    CrossrefPubMedSearch in Google Scholar
  • 30 Portolani M, Pecorari M, Tamassia M G, Gennari W, Beretti F, Guaraldi G. Case of fatal encephalitis by HHV-6 variant A.  J Med Virol. 2001;  65 133-137
    CrossrefPubMedSearch in Google Scholar
  • 31 Rantala H, Mannonen L, Ahtiluoto S, Linnavuori K, Herva R, Vaheri A. et al . Human herpes virus-6 associated encephalitis with subsequent infantile spasms and cerebellar astrocytoma.  Dev Med Child Neurol. 2000;  42 418-421
    CrossrefPubMedSearch in Google Scholar
  • 32 Razzaque A. Oncogenic potential of human herpes virus-6 DNA.  Oncogene. 1990;  5 1365-1370
    PubMedSearch in Google Scholar
  • 33 Razzaque A, Williams O, Wang J, Rhim J S. Neoplastic transformation of immortalized human epidermal keratinocytes by two HHV-6 DNA clones.  Virology. 1993;  195 113-120
    CrossrefPubMedSearch in Google Scholar
  • 34 Reifenberger G, Kros J M, Burger P C, Louis D N, Collins V P. Oligodendrogliomas. Kleihues P, Cavenee WK Pathology and Genetics of Tumours of the Nervous System. WHO Classification of Tumours. 1 - 1 - 2000. Lyon; IARC Press 2000: 38-44
    Search in Google Scholar
  • 35 Rojo J, Ferrer A V, Klueppelberg U, Krueger G R, Eidt E, Ablashi D V. et al . Semi-quantitative in situ hybridization and immunohistology for antigen expression of human herpes virus-6 in various lymphoproliferative diseases.  In Vivo. 1994;  8 517-526
    PubMedSearch in Google Scholar
  • 36 Saito Y, Sharer L R, Dewhurst S, Blumberg B M, Hall C B, Epstein L G. Cellular localization of human herpes virus-6 in the brains of children with AIDS encephalopathy.  J Neurovirol. 1995;  1 30-39
    PubMedSearch in Google Scholar
  • 37 Santoro F, Kennedy P E, Locatelli G, Malnati M S, Berger E A, Lusso P. CD46 is a cellular receptor for human herpes virus 6.  Cell. 1999;  99 817-827
    CrossrefPubMedSearch in Google Scholar
  • 38 Shanavas K R, Kala V, Vasudevan D M, Vijayakumar T, Yadav M. Anti-HHV-6 antibodies in normal population and in cancer patients in India.  J Exp Pathol. 1992;  6 95-105
    PubMedSearch in Google Scholar
  • 39 Singh N, Carrigan D R, Gayowski T, Singh J, Marino I R. Variant B human herpes virus-6 associated febrile dermatosis with thrombocytopenia and encephalopathy in a liver transplant recipient.  Transplantation. 1995;  60 1355-1357
    PubMedSearch in Google Scholar
  • 40 Wakefield A J, Fox J D, Sawyerr A M, Taylor J E, Sweenie C H, Smith M. et al . Detection of herpes virus DNA in the large intestine of patients with ulcerative colitis and Crohn's disease using the nested polymerase chain reaction.  J Med Virol. 1992;  38 183-190
    PubMedSearch in Google Scholar
  • 41 Wang F Z, Linde A, Hagglund H, Testa M, Locasciulli A, Ljungman P. Human herpes virus 6 DNA in cerebrospinal fluid specimens from allogeneic bone marrow transplant patients: does it have clinical significance?.  Clin Infect Dis. 1999;  28 562-568
    PubMedSearch in Google Scholar
  • 42 Webb D W, Bjornson B H, Sargent M A, Hukin J, Thomas E E. Basal ganglia infarction associated with HHV-6 infection.  Arch Dis Child. 1997;  76 362-364
    PubMedSearch in Google Scholar
  • 43 Yadav M, Chandrashekran A, Vasudevan D M, Ablashi D V. Frequent detection of human herpes virus 6 in oral carcinoma.  J Natl Cancer Inst. 1994;  86 1792-1794
    PubMedSearch in Google Scholar
  • 44 Yalcin S, Karpuzoglu T, Suleymanlar G, Mutlu G, Mukai T, Yamamoto T. et al . Human herpes virus 6 and human herpes virus 7 infections in renal transplant recipients and healthy adults in Turkey.  Arch Virol. 1994;  136 183-190
    CrossrefPubMedSearch in Google Scholar
  • 45 Yamanishi K, Okuno T, Shiraki K, Takahashi M, Kondo T, Asano Y. et al . Identification of human herpes virus-6 as a causal agent for exanthem subitum.  Lancet. 1988;  1 1065-1067
    PubMedSearch in Google Scholar

Tommy Stödberg

Department of Neuropediatrics, Astrid Lindgren Children's Hospital, Karolinska Hospital

17176 Stockholm

Sweden

Email: tommy.stodberg@ks.se