**3. Epidemiology**

Herpes simplex virus holds the dubious honor of being the commonest cause of acute focal encephalitis, and is thus the presumptive diagnosis in patients with viral encephalitis. How‐ ever, prospective studies have shown that about 9% have a different etiology and may be due to enteroviruses [6, 7]. Enteroviruses have a worldwide distribution, but recent out‐ breaks of EV71 have been centered in Asia, particularly East and Southeast Asia [8-16]. En‐ terovirus 71 is not the only enterovirus that involves the central nervous system (CNS). In a Canadian survey of enteroviral infections of the CNS from 1973 to 1981, coxsackie-virus A9, B1, B2, B3 and B5, echoviruses type 6, 7, 9, 11, 30, poliovirus type 2 were isolated as well [17]. The incidence of encephalitis specifically in enterovirus infections is reported to be at 3% [18], with the majority presenting meningitis.

Clinically evident infection occurs mainly in children with few cases reported in adults [19]. There is a male preponderance [19]. In children, the infection usually presents as hand, foot and mouth disease (HFMD). Yet from the late 1990s onwards, increasingly severe cases caused by enterovirus have been documented, particularly involving EV71. In adults, there have been a few case reports occurring after immunosuppressive therapy such as rituximab [20]. Rituximab is a chimeric anti-CD20 monoclonal antibody that can cause profound B-cell lymphopenia and antibody deficiency. There are 3 main different clinical neurological com‐ plications of EV71 infection; 1.flaccid paralysis and encephalitis [3, 21], 2.HFMD and menin‐ goencephalitis [22-24] and 3.HFMD or herpangina and rhombencephalitis with neurogenic pulmonary edema [16, 25-27].

The incidence of CNS complications in enterovirus infection has been reported to range from 2-10% [28]. Even so, according to a prospective study of 773 children [5] and retrospec‐ tive study of 423 patients [19], it can go as high as to 19-42%, respectively. Of the 773 chil‐ dren, EV71 was isolated in 277 (41%) and out of the 277 children, a further 28 had coinfections with a second virus (other enteroviruses, adenovirus and unidentified virus) [5]. Coxsackie A virus was isolated in 85 patients and out of these, 4 had coinfections as well. Other enteroviruses, adenoviruses or unidentified viruses were isolated in 58 [5]. While coinfections with other enteroviruses did not appear to increase the risk of neurologi‐ cal complications, an association was found between patients who were coinfected with dengue viruses and neurological symptoms [5]. Similarly, in the retrospective study of 423 patients, those with CNS involvement were more likely to have EV71 (21%) instead of cox‐ sackie A virus infection (16%). In addition, rate of disease progression and severity was re‐ ported to be greater in EV71 infection [19].
