infection with respiratory syncytial virus ( rsv ) causes bronchitis , bronchiolitis , and pneumonia , and leads to neurological complications in 1.8  % of cases . these neurological complications include rsv encephalopathy [ 2 , 3 ] , the cause of which remains unclear . kawashima et al .   defined three pathogenic types of rsv encephalopathy characterized by metabolic error , excitotoxicity , and cytokine storm . here , we describe a rare case of a neonate with rsv encephalopathy of the cytokine storm type , which involved development of pediatric systemic inflammatory response syndrome ( sirs ) and prolonged hypoperfusion lesions on brain single - photon emission computed tomography ( spect ) without neurological sequelae . the patient was a male infant born at 39  weeks gestation ( birth weight , 3,562  g ) . at this time , his brother and cousin both had a cold , and the patient presented with rhinorrhea and cough after several days . at 17  days of age , his parents brought him to the emergency department because of poor sucking for more than half a day and hypothermia ( 33.0  c ) . the patient was in a continuous stupor with hypotonia and did not respond to pain . laboratory findings upon admission showed increased aspartate aminotransferase ( ast ) , alanine aminotransferase ( alt ) , lactase dehydrogenase ( ldh ) , creatine phosphokinase ( cpk ) , and carbon dioxide ( paco2 ) ( table  1 ) . ast , alt , ldh , and cpk levels in serum increased progressively until day 2 . rsv antigen was detected in a nasopharyngeal swab . chest radiography and computed tomography scans showed bilateral pulmonary infiltrative shadow , atelectasis , and severe air trapping . a diagnosis of pediatric sirs caused by rsv infection was made based on the published criteria for this condition .table 1laboratory data at admissionperipheral bloodarterial blood gas analysis ( fio2 0.300.45 )  wbc20,200/l  ph7.228  nt31  %  paco2 
 69.4  torr  ly47  %  pao2 
 72.7  torr  mo10  %  hco3 
 27.9  mmol / l  eo2  %  be0.1  meq / l  ba0  % serology  rbc305    10/l  crp3.87  mg / dl  hb10.1  g / dl  procalcitonin0.77  ng / ml  ht32.4  %  igg853  mg / dl  plt52.7    10/l  igm32  mg / dlbiochemistry  iga5  mg / dl  tp6.7  g / dl  ferritin8163  ng / ml  alb4.1  g / dl  il-6 ( < 4  pg / ml ) 
 304  pg / ml  ast192  u / lserology during hospitalization  alt160  u / l  il-1 ( < 10  pg / ml ) 
 < 200  pg / ml  t - bil1.3  mg / dl  il-8 ( < 2  pg / ml ) 
 115  pg / ml  ldh1359  u / l  il-10 ( < 5  pg / ml ) 
 < 20  pg / ml  ck439  u / l  mcp-1 ( 200722  pg / ml ) < 625  pg / ml  bun12  mg / dl  tnf- ( 0.62.8  pg / ml ) 
 < 5  pg / ml  cre0.24  mg / dlcerebral spinal fluid  na122  meq / l  il-6 ( < 0.4  pg / ml ) 
 102  pg / ml  k5.8  meq / l  viral culture( )  cl89  meq / l  protein88  mg / dl  glucose55  g / dl  cell count2/lculture  blood()  spinal fluid()  nasal 
 haemophilus influenzae 
  
 normal value or range . il-6 was measured using human il-6 cleia ( fujirebio , japan ) . il-1 , il-8 , and il-10 were measured using biosource il-1 , il-8 , and il-10 elisa kits ( biosource europe , nivelles , belgium ) . mcp-1 and tnf- were measured using human mcp-1 and tnf- immunoassay kits ( r&d systems , minneapolis , mn , usa ) laboratory data at admission 
 normal value or range . il-1 , il-8 , and il-10 were measured using biosource il-1 , il-8 , and il-10 elisa kits ( biosource europe , nivelles , belgium ) . mcp-1 and tnf- were measured using human mcp-1 and tnf- immunoassay kits ( r&d systems , minneapolis , mn , usa ) the patient was intubated and ventilated immediately . immunomodulatory therapy with high - dose steroids ( methylprednisolone 30  mg / kg / day for 3  days ) was also initiated because the respiratory therapies were ineffective . on day 5 , there were no significant abnormalities on t1-weighted , t2-weighted , and fluid - attenuated inversion recovery magnetic resonance imaging ( mri ) , but the bilateral hippocampus showed a high signal intensity in diffusion - weighted imaging ( dwi ) mri with reduction of the apparent diffusion coefficient ( adc ) ( fig .  1 a , b ) . diffusion - weighted imaging ( dwi ) ( a ) revealed bilateral high - intensity regions in the hippocampus , and the apparent diffusion coefficient ( adc ) ( b ) was low in the same regions . c  f 
 tc- ethylcysteinate dimer ( ecd ) single - photon emission computed tomography ( spect ) . axial views through the parietal lobes ( c , e ) and through the cerebral cortex , white matter , and basal ganglia ( d , f ) . upper row ( c , d ) : at 18  days after onset ( hospital day 18 ) , spect showed hypoperfusion of the bilateral frontal and parietal lobes and the unilateral temporal lobe with some predominance on the left side . lower row ( e , f ) : at 3  months after onset , hypoperfusion of the bilateral parietal lobes on spect had improved , but hypoperfusion of the unilateral temporal lobe with some predominance on the left side was exacerbated magnetic resonance imaging ( mri ) on day 6 . diffusion - weighted imaging ( dwi ) ( a ) revealed bilateral high - intensity regions in the hippocampus , and the apparent diffusion coefficient ( adc ) ( b ) was low in the same regions . f 
 tc- ethylcysteinate dimer ( ecd ) single - photon emission computed tomography ( spect ) . axial views through the parietal lobes ( c , e ) and through the cerebral cortex , white matter , and basal ganglia ( d , f ) . upper row ( c , d ) : at 18  days after onset ( hospital day 18 ) , spect showed hypoperfusion of the bilateral frontal and parietal lobes and the unilateral temporal lobe with some predominance on the left side . lower row ( e , f ) : at 3  months after onset , hypoperfusion of the bilateral parietal lobes on spect had improved , but hypoperfusion of the unilateral temporal lobe with some predominance on the left side was exacerbated on day 14 , the hippocampal abnormality and adc were improved on dwi mri . however , on the same day , the patient presented with trembling of the upper limbs from side to side , and an eeg showed occasional unilateral spikes in the parietal area . therefore , anticonvulsant therapy with phenobarbital was started . barr virus , herpes simplex virus , and autoantibodies associated with limbic encephalitis ( antibodies against the glutamate receptor glu2 , voltage - gated potassium channel , and nr1/nr2 subunits of the n - methyl - d - aspartate receptor ) were negative during the acute phase . interleukin ( il)-6 was increased markedly in the spinal fluid , and il-6 serum levels were even more elevated compared with the spinal fluid [ 2 , 3 ] . in the acute phase , serum il-8 was significantly and markedly increased , but il-1 , il-10 , monocyte chemoattractant protein ( mcp)-1 , and tumor necrosis factor ( tnf)- levels were only slightly increased or not significantly altered ( table  1 ) . therefore , the patient was diagnosed with encephalopathy caused by rsv infection , as suggested by a prior study showing stupor and hypotonia lasting for at least 24  h and seizure . tc - labeled ethylcysteinate dimer ( ecd ) spect on hospital day 18 showed hypoperfusion of the bilateral frontal and parietal regions and the unilateral temporal region with some predominance on the left side ( fig . 1c , d ) . follow - up eeg , mri , and spect were performed 3  months after onset . tc - labeled ecd spect at 3  months still showed hypoperfusion of the bilateral frontal region and unilateral temporal region with some predominance on the left side . hypoperfusion on spect had improved in the bilateral parietal lobes but persisted in the frontal and temporal regions ( fig .  1e , f ) . the present case was diagnosed as rsv encephalopathy accompanied by markedly increased levels of serum il-6 . these findings are consistent with alteration of cytokine levels in influenza virus - associated encephalopathy , because previous studies have shown marked increases of il-6 in serum and spinal fluid in this disease [ 7 , 8 ] . in particular , the serum il-6 level has been suggested to be a useful indicator for the diagnosis and clinical severity of viral encephalopathy . in our case , spinal fluid il-6 was increased significantly and serum il-6 showed an even greater increase . however , we also note that some studies have not found increased serum il-6 in rsv encephalopathy [ 24 ] . the cause of sirs is essentially overproduction of inflammatory cytokines such as tnf- , il-1 , and il-6 . thus , sirs associated with rsv infection may be characterized by progression of severe pneumonia caused by hematogenous actions of elevated il-6 on the lung and encephalopathy of the cytokine storm type resulting from similar actions of il-6 on the brain . this suggestion is supported by the marked increase in serum il-8 , which is similar to the cytokine storm that can occur in influenza virus - associated encephalopathy . the elevated il-6 levels in the spinal fluid and serum and elevated il-8 levels in the serum suggest that cytokine storm may be involved in the pathogenesis of rsv encephalopathy . however , the etiology of rsv encephalopathy is unclear . specifically , it is uncertain whether direct impairment of the central nervous system is primarily responsible for the cerebral involvement in rsv disease , or if this is caused by increased production of one or more cytokines in cerebrospinal fluid during the acute phase [ 11 , 12 ] . a recent report showed that these findings often include unilateral brain hemisphere abnormalities on ct , mri , and spect [ 3 , 11 , 13 ] . our case exhibited hypoperfusion of the bilateral hippocampal regions and the unilateral temporal region on spect . in general , limbic encephalitis associated with infection is most commonly caused by herpes simplex virus , but a test for herpes simplex virus igm antibody was negative on day 12 . most cases of autoimmune limbic encephalitis are indicated by autoantibodies , but in this case these autoantibodies were negative or normal in the acute phase . showed that hippocampal dwi hyperintensities and a reduction of adc on mri were caused by limbic encephalitis with viral infection . therefore , this patient was diagnosed with rsv encephalopathy without limbic encephalitis . after 3  months , hypoperfusion on spect had improved in the bilateral parietal lobes , but persisted in the frontal and temporal regions without neurological sequelae . .   found that residual cerebellar abnormalities on spect persisted 1  year after onset in rsv encephalitis with mild ataxia . our case suggests that detection of severe rsv infection should lead to consideration of an early diagnosis of encephalopathy associated with sirs .
respiratory syncytial virus ( rsv ) is a cause of neurological complications in infants . 
 we report a rare case of rsv encephalopathy in an infant who presented with poor sucking and hypothermia at 17  days of age after suffering from rhinorrhea and a cough for several days . after hospitalization , 
 the patient presented with stupor and hypotonia lasting for at least 24  h , and was intubated , sedated , and ventilated for treatment of pneumonia . 
 these symptoms led to diagnosis of pediatric systemic inflammatory response syndrome ( sirs ) caused by rsv infection . 
 high - dose steroid therapy was combined with artificial ventilation because the initial ventilation therapy was ineffective . 
 interleukin ( il)-6 levels in spinal fluid were markedly increased upon admission , and serum il-6 and il-8 levels showed even greater elevation . the patient was diagnosed with rsv encephalopathy . on day 5 , high signal intensity in the bilateral hippocampus was observed on diffusion - weighted magnetic resonance imaging ( mri ) . on day 14 
 , the patient presented with delayed partial seizure and an electroencephalogram showed occasional unilateral spikes in the parietal area , but the hippocampal abnormality had improved to normal on mri . 
 99mtc - labeled ethylcysteinate dimer single - photon emission computed tomography ( spect ) on day 18 showed hypoperfusion of the bilateral frontal and parietal regions and the unilateral temporal region . 
 spect at 3  months after onset still showed hypoperfusion of the bilateral frontal region and unilateral temporal region , but hypoperfusion of the bilateral parietal region had improved . 
 the patient has no neurological deficit at 6  months . 
 these findings suggest that rsv encephalopathy with cytokine storm induces several symptoms and complications , including sirs and prolonged brain hypoperfusion on spect .