Abstract
Most febrile convulsions (FC) in infants occur during a viral infection, particularly in children of less than 3 years of age; human herpesvirus 6 (HHV-6) has an important pathogenic role. To evaluate the link between this and other viruses and FC, a group of 65 children (mean age 18.46 months, SD±9.19) with a first episode of simple FC (G1) was compared with 24 children (mean age 19.29 months, SD±13.17) with a febrile syndrome but without FC (G2). Virological study showed the following infection: HHV-6 in 23/65 of G1 and in 12/24 of G2, adenoviruses (ADV) in 9/65 of G1 and in 0/24 of G2, syncytial respiratory virus (SRV) in 3/28 of G1 and in 0/2 of G2, HSV-1 in 6/65 of G1 and in 1/24 of G2, cytomegalovirus (CMV) in 2/65 of G1 and in 0/24 of G2 and HHV-7 in 1/42 of G1 and in 1/13 of G2. Children in G1, statistically compared with G2, were significantly more likely to have a family history of FC and circulating granulocytes, while IgM and α2-globulin were less probable. Some cytokines (IL1β, TNFβ and GM-CSF) were found in 24 children in G1 and 12 in G2; no differences were found between the two groups. In the light of our data and of the recent literature, the possibility that the cytokines may act on the nervous system cannot be excluded. Among the HHV-6-infected children, those suffering from convulsions were statistically more likely to have a family history of FC and IgM, while IgA were less likely. In G1, 57 cases were followed up over 2 years: 9 of them had a second episode of FC. Virological diagnosis at the first episode of FC revealed HHV-6 infection in 3 cases, 2 of these being due to viral reactivation. We underline the important role of HHV-6 infection in FC and postulate a relationship between family history and the immunity of the patient; this is confirmed by the loss of statistical significance in the reduction of IgM in G1 compared with G2 with no family history of FC. The reactivation of FC by HHV-6 is a possibility to be borne in mind; an increased number of cases would be needed to confirm this hypothesis.
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Asano Y, Yoshikawa T, Suga S, Kobayashi I, Nakashima T, Yazaki T, Kajita Y, Ozaki T (1994) Clinical features of infants with primary human herpesvirus 6 infection (exanthem subitum, roseola infantum). Pediatrics 93:104–108
Bertolani MF, Marotti F, Guaraldi C, Portolani M, Cermelli C, Pecorari M, Sabbattini AM (1991) Convulsioni febbrili ed infezione da Herpes virus-6. Acta Paediatr Lat 44:234–241
Carrigan DR, Drobyski WR, Russler SK, Tapper MA, Knox LK, Ash RC (1991) Intersititial pneumonitis associated with human herpesvirus-6 infection after marrow transplantation. Lancet 338:147–149
Cavazzuti GB (1984) Le convulsioni febbrili che evolvono in epilessia. Riv Ital Pediatr 10:470–473
Chamberlain JM, Gorman RL (1988) Occult bacteremia in children with simple febrile seizures. Am J Dis Child 142:1073–1076
Consensus Development Conference on Febrile Seizures (1981) Proceedings of the Conference held at the National Institutes of Health, 19–21 May 1980. Epilepsia 22:377–381
Familusi JB, Sinnette CH (1971) Febtile convulsions in Ibadan children. Afr J Med Sci 2:135–150
Fischler E (1962) Convulsions as a complication of shigellosis in children. Helv Pediatr Acta 17:389–394
Flamand L, Gosselin J, D'Addario M, Hiscott J, Ablashi DV, Gallo RC, Menezes J (1991) Human herpesvirus 6 induces interleukin-1b and tumor necrosis factor alpha, but not interleukin-6, in peripheral blood mononuclear cell cultures. J Virol 65:5105–5110
Hauser WA (1981) The natural history of febrile seizures. In: Nelson KB, Ellemberg JH (eds) Febrile seizures. Raven Press, New York
Helminen M, Vesikari T (1990) Increased Interleukin-I (IL-1) production from LPS-stimulated peripheral blood monocytes in children with febrile convulsions. Acta Paediatr Scand 89:810–816
Horvat RT, Parmely MJ, Chandran B (1993) Human herpesvirus 6 inhibits the proliferative responses of human peripheral blood mononuclear cells. J Infect Dis 167:1274–1280
Ishiguro N, Yamada S, Takahashi T, Takahashi Y, Togashi T, Okumo T, Yamanishi K (1990) Meningo-encephalitis associated with HHV-6 related exanthem subitum. Acta Paediatr Scand 79:987–989
Kikuta H, Nakane A, Lu H, Taguchi Y, Minagawa T, Matsumoto S (1990) Interferon induction by human herpesvirus 6 in human mononuclear cells. J Infect Dis 162:35–38
Kondo K, Nagafuji H, Hata A, Tomomori C, Yamanishi K (1993) Association of human herpesvirus 6 infection of the central nervous system with recurrence of febrile convulsions. J Infect Dis 167:1197–1200
Lewis HM, Parry JV, Parry RP, Davies HA, Sanderson PJ, Tyrrell DAJ, Valman HB (1979) Role of viruses in febrile convulsions. Arch Dis Child 54:869–876
Luppi M, Barozzi P, Maiorana A, Marasca R, Torelli G (1994) Human herpesvirus 6 infection in normal human brain tissue. J Infect Dis 169:943–944
Merrill JE (1992) Tumor necrosis factor alpha, interleukin 1 and related cytokines in brain development: normal and pathological. Dev Neurosci 14:1–10
Newmark ME, Penry JK (1980) Genetics of epilepsy: a review. Raven Press, New York
Offringa M, Bossuy PMM, Lubsen J, Ellemberg JH, Nelson KB, Knudsen FU, Annegers JF, El-Rahdi AS, Habbema JD, Derksen-Lubsen G, Hauser WA, Kurland LT, Banajeh SMA, Larsen S (1994) Risk factors for seizures recurrence in children with febrile seizures: a pooled analysis of individual patient data from five studies. J Pediatr 124:574–584
Portolani M, Cermelli C, Pietrosemoli P, Pecorari M, Farabegoli F, Cavazzuti GB, Bertolani MF, Micheli A (1990) Isolation of HHV-6-related virus from children affected by infectious syndrome. Arch Virol 110:143–149
Suga S, Yoshikawa T, Asano Y, Kozawa T, Nakashima T, Kobayashi I, Yazaki T, Yamamoto H, Kajita Y, Ozaki T, Nishimura Y, Yamanaka T, Yamada A, Imanishi J (1993) Clinical and virological analyses of 21 infants with exanthem subitum (roseola infantum) and central nervous system complications. Ann Neurol 33:597–603
Yoshikawa T, Nakashima T, Suga S, Asano Y, Yazaki T, Kimura H, Morishima T, Kondo K, Yamanishi K (1992) Human herpes virus 6 DNA in cerebrospinal fluid of a child with exanthem subitum and meningoencephalitis. Pediatrics 89:888–890
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Bertolani, M.F., Portolani, M., Marotti, F. et al. A study of childhood febrile convulsions with particular reference to HHV-6 infection: pathogenic considerations. Child's Nerv Syst 12, 534–539 (1996). https://doi.org/10.1007/BF00261607
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DOI: https://doi.org/10.1007/BF00261607