in november 2006 , a 37-year - old woman without serious past illness sought treatment at our hospital with hand tremor , unsteadiness , and a 2-day history of headache ( day 1 ) . examination showed high fever ( 39.3c ) , neck stiffness , intentional tremor of bilateral upper extremities , and truncal ataxia . brain magnetic resonance images ( mri ) and results of laboratory blood tests were normal . a cerebrospinal fluid ( csf ) tap showed 305 leukocytes / mm ( 82.5% polymorphonuclear leukocytes and 17.5% lymphocytes ) and total protein concentration of 62 mg / dl with normal glucose levels . empirical therapy with acyclovir and cefotaxime was initiated . on day 4 , the patient reported diplopia and slurred speech . brain mri showed hyperintense lesions in the tegmentum of the medulla oblongata , pons , and midbrain in t2-weighted and fluid attenuated inversion recovery images ( figure 1 ) . results of nerve conduction studies were within normal ranges except for the absence of an f - wave in the median and ulnar nerves . methylprednisolone ( 1 g / day ) was administered for 3 days . from day 5 and a csf tap on day 15 showed 14 leukocytes / mm ( 100% lymphocytes ) and a total protein concentration of 50 mg / dl . on day 22 a ) hyperintense lesions in the tegmentum of the pons in the axial section of the fluid - attenuated inversion recovery image . b ) in the sagittal section of the t2-weighted image , hyperintense lesions are present in the tegmentum of the midbrain , pons , and medulla oblongata . during the illness , enterovirus - specific rna was detected from a stool sample on day 16 by a seminested reverse transcription pcr ( rt - pcr ) with consensus - degenerative primers from nix et al . ( 5 ) ; the virus was identified as ev71 by sequence analysis of the partial vp1 region ( 5 ) . serum neutralizing antibody titer against ev71 increased , from 8 on day 1 to 128 on day 15 . there was no increase in serum antibodies against other viruses , including herpes simplex virus , cytomegalovirus , varicella - zoster virus , epstein - barr virus , rubella virus , and mumps virus by enzyme immunoassay , and against japanese encephalitis virus by hemagglutination - inhibition test . three days before the patient sought treatment , her 1-year - old son was affected with hfmd . this disease also developed in her other 2 sons , 5 and 7 years of age , on day 2 . enterovirus - specific rna was also detected in the stool samples from the 3 children by seminested rt - pcr ( 5 ) , and all 3 viruses were identified as ev71 by sequence analysis . in addition , ev71 was isolated in vero cells from stool samples from 2 of the 3 sons with hfmd . stool and other clinical samples from the mother were all negative for virus isolation on vero and rd cells . the partial vp1 sequences ( 150 bp ) of the pcr products directly amplified from stool samples of all 4 cases were 100% identical . the entire vp1 sequences ( 891 bp ) of the ev71 isolates from 2 of her sons with hfmd ( 07-ishikawa and 08-ishikawa ) were also 100% identical . phylogenetically , by using vp1-based genetic classification , the isolates were classified as subgenogroup c4 ( figure 2 ) ( 6 ) . the subgenogroup c4 of ev71 has recently been identified in japan and might have emerged in the surrounding countries , mainland people s republic of china and taiwan ( 69 ) . the 07-ishikawa strain shows a close genetic relationship to recent subgenogroup c4 strains in mainland china ( 97.4% nt identity to the shzh0438 strain ) and those in japan ( 97.0% nt identity to the 2779-yamagata strain , figure 2 ) ( 7,9 ) . the tree was prepared by the neighbor - joining method by using the ev71 strains in the world as described previously ( 6 ) and newly identified subgenogroup c4 strains ( 7,8 ) were also included in the analysis . several ev71 outbreaks have been documented throughout the world , and clinical manifestations of ev71 infections can be diverse , including hfmd , herpangina , central nervous system ( cns ) complications , and pulmonary edema . recently , ev71-associated hfmd outbreaks with severe cns complications have frequently been reported , especially in the asian - pacific region ( 2,3 ) . in children , the cns complications associated with ev71 manifest clinically in various ways , such as aseptic meningitis , acute flaccid paralysis , and rhombencephalitis ; we diagnosed the mother s illness as ev71 encephalitis because the clinical features were similar to those of ev71 rhombencephalitis in children ( 2,10 ) , although there has not previously been a detailed case report of adult - onset ev71 encephalitis . ev71 was not identified in the mother s csf sample by virus isolation or direct molecular detection by rt - pcr , but ev71 was identified in her stool sample . we could not exclude the possibility of para- or post - infectious encephalitis during the initial stage of her illness . however , rhombencephalitis subsequently developed in this patient , which is common in children with ev71 encephalitis but is far less common from other infections and para- or post - infectious encephalitis . clinical symptoms , mri , and csf findings of her illness were similar to those reported in children with ev71 encephalitis . several previous studies have demonstrated a rather low virus isolation rate in cns specimens compared with that in other clinical samples , such as throat swab , rectal swab , and stool samples from ev71-associated cases with hfmd , encephalitis , or both ( 2,3,11 ) . along with the identification of ev71 , the increase in serum neutralizing antibody titer against ev71 supports the diagnosis of acute ev71 infection . in addition , the lack of abnormalities of the spinal cord on mri , the absence of an f - wave on nerve conduction study ( a possible sign of radiculopathy ) , and the absence of deep tendon reflexes without weakness support the possibility of radiculitis as a complication . in a previous report , some patients with rhombencephalitis showed hyporeflexia or areflexia , but nerve conduction study findings were not reported ( 2 ) . genetic analysis among 4 different ev71 isolates from the patients indicated probable intrafamilial transmission of ev71 . in a recent study , ev71 transmission rate to household contacts was 52% , and twenty - one percent of ev71-infected children experienced serious complications , including cns or cardiopulmonary failure . by contrast , 53% of adults were asymptomatic , and all symptomatic adults recovered completely from uncomplicated illnesses ( 4 ) . considerable attention has been paid to ev71 infection in children because young age was considered the major risk factor associated with severe cns complications , such as encephalitis resulting in severe neurologic sequelae and deaths ( 24,12 ) . our patient showed a good prognosis ; however , a 19-year - old man died from ev71 encephalitis in singapore ( 3 ) . more careful disease surveillance , even for adults ,
enterovirus 71 ( ev71 ) is a common cause of hand , foot , and mouth disease and sometimes causes severe neurologic complications , mainly in children . 
 we report a case of adult - onset encephalitis caused by intrafamilial transmission of a subgenogroup c4 strain of ev71 . 
 this case elucidates the risk for ev71 encephalitis even in adults .