Korean J Pediatr 2010;53(5):616-622 • DOI: 10.3345/kjp.2010.53.5.616 619 predominantly caused by strains that are distinct from previous outbreaks27). In Singapore, since the first outbreak of HFMD in 1970, many epidemics have occurred by predominantly circulating strain coxsackievirus A16 or EV71, and the largest one was caused by EV71 with 3,790 cases and four deaths in 200013, 28). In 2006, Brunei reported that 1,681 children were affected with three deaths resulting from severe neurologic disease6). In the same year, an outbreak of EV71 affected approximately 14,400 children in Sarawak, Malaysia29). In the outbreak of China in 2008, a total of 488,955 HFMD cases were reported including 126 fatal cases, mostly caused by EV717). Possible reasons suggested for the outbreaks were mutation of the virus with increased virulence and the presence of host factors including the accumulation of susceptible populations and individual genetic susceptibility30, 31). Ooi et al32) studied about the clinical risk factors to help detect children at risk of neurological involvement. They noticed that total duration of fever >or= 3 days, peak temperature >or= 38.5°C and history of lethargy were independent risk factors for neurological involvement. Mortality was high in EV71 brainstem encephalitis complicated with pulmonary edema, particularly in children below 5 years of age. There have been several large epidemics of EV71 infection causing high fatalities. The first report of severe epidemics of encephalitis and acute flaccid paralysis due to EV71 came from Bulgaria in 1975, in which 44 deaths occurred33). In 1978, 45 patients died of neurologic diseases with HFMD in Hungary34). Since 1997, three major epidemics have occurred in the Asia-Pacific region. They were in Sarawak, Malaysia in 1997, Taiwan in 1998, and China in 2008, and 31, 78, and 126 fatal cases were reported, respectively7, 24, 35). In Korea, EV71 were isolated for the first time from 12 patients with hand foot mouth disease on 2000 laboratory surveillance. During 2009 outbreaks in Korea, about 90 % isolates were from patients with HFMD and 10% from those with herpangina. Most patients with EV71 who presented neurologic symptoms were associated with HFMD. They were diagnosed as meningitis or meningoencephalitis, and Guillain-Barré syndrome, poliomyelitis- like paralytic disease and myoclonus. Gene analysis showed that most of them were caused by EV71 subgenotype C4a, which was prevalent in China in 2008. EV71 infections with severe cases with complications including death become a public health issue1). During 2009 outbreaks in Korea, 16 patients were hospitalized with neurologic manifestations related with HFMD at Ewha Womans University Mokdong Hospital (Table 2). Their ages ranged from a month to eight years and the mean age was 29 months. The male to female ratio was 1.7:1 (M:F). Fever resolved in 2 to 7 days (mean, 4.5 days) and the range of peak of fever was 38.0 to 40.1°C (mean, 39.3°C). In most of the patients, neurologic symptoms developed between day 2 and day 3 (range, day 1 to day 5) after the onset of fever or skin lesions. Among the 16 patients, the most frequent neurologic manifestation was meningitis (62.5%), which included 8 definite cases with meningeal irritative symptoms and signs with CSF pleocytosis (>5 cells/mm3) and 2 suspected cases in whom spinal tappings were not performed. Three cases had Guillain-Barré syndrome and one of them had meningoencephalitis. One patient presenting asymmetric lower limb weakness (left>right) after HFMD showed enhancement in the left anterior horn of the spinal cord (T11 level) on magnetic 1 F 42 2 M 21 3 M 8 4 F 21 5 M 83 6 F 18 7 M 34 8 F 33 9 F 18 10 M 27 11 M 1 12 M 1 13 M 8 14 F 102 15 M 41 16 M 3 Abbreviations : ND, not done; UT, untypable Table 2. Clinical Features of Patients with Enterovirus 71 Associated Neurological Disease in Ewha Womans University Mokdong Hospital No. Sex (mAongtehs) Clinical presentation EV71CpSoFsitivity in clinicaSl tsoaomlple CS(Fceplllse/omcmyto3)sis Meningitis ND + ND Myoclonus ND + ND Guillain-Barré syndrome - + 14 Poliomyelitis-like paralysis - + 48 Meningitis - + 60 Meningitis - + 880 Meningitis, convulsion - + 110 Meningitis - + 14 Guillain-Barré syndrome - + 40 Meningitis ND + ND Meningitis - + 8 Meningitis - + 160 Guillain-Barré syndrome - + 70 Meningoencephalitis - + 20 Meningitis - + 70 Meningitis - + 11 Subgenotype of EV71 C4a C4a C4a C1 C4a C4a C4a C4a C4a UT UT UT C4a UT C4a C4a