A patient characterized by coma or seizure following hyperpyrexia might be diagnosed as having common febrile convulsions. However, when such a patient also presents with elevated liver enzymes and CK upon admission, hypotension within 24 hours after admission, with refractory acid-base disturbance and an abnormally high serum lactate level, even with fluid-resuscitate and/or vasopressor infusion, these signs may be useful markers for an early HSES diagnosis and indicators to start intensive neurological treatment. HSES is not a disease that can be diagnosed easily using the current diagnostic criteria, however, HSES can be predicted in the early stage of its clinical course using these new prodromal diagnostic markers.