Charts of children with febrile seizures admitted to the Hospital of Shiga University of Medical Sciences, Otsu, Japan, 2006-2007, were reviewed retrospectively. Clinical characteristics of 23 patients who received antihistamines were compared with 26 with no antihistamines. No significant difference was observed in sex ratio, age, family history of febrile seizures or epilepsy, cause of fever, and proportion of simple and complex febrile seizures between antihistamine and non-antihistamine groups. In the antihistamine group, time from fever detection to seizure onset (simple and complex separately or together) was significantly shorter (P<0.001), and seizure duration was significantly longer (P<0.05). Seizure types and EEG abnormalities were similar in the two groups. Hypothalamic neuronal histamine depletion induced by antihistamines may lower febrile seizure threshold and increase seizure susceptibility. 
COMMENT. This clinical study supports the significance of many prior laboratory experiments that demonstrate an increase in seizure susceptibility following antihistamine administration. The febrile seizure threshold temperature was lowered and severity of experimental seizures exacerbated in animals following diphenhydramine administration . West syndrome has been associated with antihistamines in Japan (Yasuhara A et al, 1998; Yamashita Y et al, 2004). Patients with seizures should be cautioned to avoid antihistamine medications when possible.