Influenza virus and febrile convulsions.

To the Editor—Recently, Kawada et al. [1] described systemic cytokine responses in infants and children with influenza-associated encephalopathy and febrile convulsions (FCs). The authors suggested that the pathogenesis of FCs is similar to that of encephalopathy and that the differentiation of encephalopathy and complex FCs may be difficult. The mechanism of FCs is a controversial topic, and the perspective of a pediatric neurologist with a long-time interest in FCs (J.G.M.) may be appropriate. Influenza A virus is a frequent cause of FCs in Japan [1] and in other Asian countries. In Hong Kong, influenza A virus infection accounted for up to 35%–44% of hospital admissions for FC during peak influenza months in 1997 and 1998, a much higher incidence than for FCs associated with parainfluenza and adeno-virus infection [2]. In contrast, except for 1 epidemic in the United Kingdom in 1972 [3], influenza A virus is an uncommon cause of FCs in western Europe and the United States. Among 6790 patients worldwide with FCs reported in 33 publications between 1929 and 1964 (none from Japan), the causes of fever were noted for a total of 7036 febrile episodes, and the prevalence of the various infections was tabulated [4]. Apart from roseola infantum in 1.4% of cases, viral infections as a cause of FCs were rarely reported in the first half of the twentieth century, and influenza virus infection was not recorded. In the United States, infection with human herpesvirus (HHV)–6 is a more frequent cause of FCs than is infection with influenza A virus and accounts for one-third of all first-time febrile seizures in children р2 years old [5]. The risk of FCs due to HHV-6 infection is 29% (for HHV-6 associated with roseola, the risk of FCs is 17%), compared with a risk of only 9% due to non–HHV-6 infection. The risk of FCs due to HHV-6 infection is correlated with a high fever and with low levels of im-munoglobulin. FCs due to HHV-6 may be complex, and, like those due to influenza infection, a possible encephalitis/encepha-lopathy is suspected in some cases [4, 6]. Infections play a role in the etiology of FCs by у1 mechanism: (1) the degree of fever per se, (2) an abnormal immune state and allergic response to infection, (3) the presence of a neurotropic bacterial toxin (e.g., Shigella dysenteriae) or neu-rotropic virus (e.g., HHV-6 or influenza A virus), or (4) an unrecognized mild viral …