Ignite Creation Date:
2024-05-05 @ 11:55 AM
Last Modification Date:
2024-10-26 @ 9:16 AM
Study NCT ID:
NCT00172393
Status:
UNKNOWN
Last Update Posted:
2006-10-04
First Post:
2005-09-12
Brief Title:
Long Term Outcomes of EV71 CNS Infection
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
Long Term Outcomes of EV71 Central Nervous System Infection
Status:
UNKNOWN
Status Verified Date:
2005-06
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Our study involved 142 children with EV71 CNS infections that included 61 43 with viral meningitis 53 37 with severe CNS involvement including encephalitis polio-like syndrome and encephalomyelitis and 28 20 with cardiopulmonary failure after CNS involvement These children were subjected to physical and neurological examinations 285 range 10-739 years after disease onset Those below the age of 6 years took the Denver developmental screening test while those 4 years and over took the intelligence quotient IQ test
Detailed Description:
For the purposes of our study we identified all the EV71 pediatric patients at Chang Gung Childrens Hospital CGCH and at the NTUH between 1998 and 2003 These patients were clinically confirmed to have hand foot and mouth disease HFMD of herpangina or febrile illness and a positive laboratory-confirmed EV71 infection The EV 71 infection was confirmed on the basis of a positive viral isolation of EV71 andor a positive EV71 IgM andor a four-fold rise in EV71 neutralizing antibody serotiters between the acute and the convalescent sera
This study involved 621 EV71 patients in total 534 of them at the CGCH and 87 of them at the NTUH Of these 232 cases 374 had CNS involvement The clinical severity of the EV71 CNS involvement was classified in terms of the increasing severity of the infection Group 1 cases with mild CNS involvement ie aseptic meningitis Group 2 cases with severe CNS involvement including encephalitis polio-like syndrome or encephalomyelitis and Group 3 cases with cardiopulmonary failure after central nervous system involvement Patients placed in Group 1 were those experiencing headaches irritability and CSF pleocytosis 5x106 leukocytesL but no altered level of consciousness or focal signs Patients placed in Group 2 were encephalitis with an altered level of consciousness plus CSF pleocytosis poliomyelitis-like syndrome with acute limb weakness and decreased reflex and muscle strength and encephalomyelitis with the occurrence of both encephalitis and poliomyelitis-like syndrome Patients placed in Group 3 were those who had experienced cardiopulmonary failure defined as a decreased ejection fraction of the left ventricle as assessed by echocardiography with or without pulmonary edemahemorrhage necessitating inotropic agent and ventilator support Patients who experienced cardiopulmonary failure after CNS involvement have been found to have had a sudden onset of cardiopulmonary failure several hours or several days after the manifestations of their EV71 CNS infections516 Of these 232 cases with CNS involvement 25 108 patients died of cardiopulmonary failure and brainstem encephalitis during acute illness 19 of these 25 patients died within 7 days of the onset of acute illness while 14 60 patients died due to a deep coma or aspiration pneumonia during the convalescent stage ie more than one month after onset of their disease
Of the remaining 193 patients with CNS involvement 172 of these at the CGCH and 21 of these at the NTUH 22 refused to be assessed and 29 could not be located This means that a total of 142 736 patients were enrolled in our study and took the assessment between January 2003 and December 2005 after informed consent was obtained from their parents Figure 1 The clinical severity and the demography of the 142 patients who were assessed and the 51 patients who were not assessed p022 for clinical severity p033 for their age of onset and p035 for genders were similar It is therefore clear that the size of the study population involving these 142 patients is representative of the 193 EV71 patients with CNS involvement
Clinical and neurological outcome and neurodevelopment assessment All the children were physically and neurologically examined by a pediatrician or a pediatric neurologist during an outpatient visit or during their stay at chronic respiratory centers Their physical handicap or neurological sequelae the requirement of ventilator support and the need of tube feeding were recorded
EV71 patients who were younger than 6 years of age during our assessment were tested with the Denver Developmental Screening Test DDST II The DDST II has four categories gross motor fine motor language and personal-social17 Each test item was scored as either passed or failed The overall assessment of each child was considered normal when the child passed tasks in 25-75 for hisher age or delayed when the child failed tasks to the left of hisher age line
Cognitive function assessment The Wechsler Intelligence Scale for Children-Third Edition WISC-III Wechsler 1991 profile was individually assessed by a child psychologist for all children over four years of age except for 3 of the children who had tracheostomy and could not talk The WISC-III is a widely used measure of general intelligence for children aged 4-16 years The WISC-III is composed of 13 subtests to test childrens cognitive ability of different dimensions which are grouped into two scores the performance IQ score and the verbal IQ score The Performance IQ score 7 subtests includes Picture Completion Block Design Object Assembly Picture Arrangement Coding Symbol Search and Mazes subtests The Verbal IQ score 6 subtests includes Information Comprehension Arithmetic Similarities Digit Span and Vocabulary subtests18 Four factorially derived composite subscales have been created 1 Verbal Comprehension Information Similarities Vocabulary and Comprehension 2 Perceptual Organization Picture Completion Picture Arrangement Block Design and Object Assembly 3 Freedom From Distractibility Arithmetic and Digit span and 4 Process Speed Coding and Symbol Search 18 Each of the IQ scores and four composite subscales yield standard scores with a mean of 100 and a standard deviation SD of 15
Statistical Analysis Data were analyzed with the SAS Statistical Package Version 91 SAS Institute Cary North Carolina Data are expressed as mean SD median range or number percentage The Chi-square test was used for categorical data and the student t-test and analysis of variance ANOVA were used for continuous variables with normal distribution The Mann-Whitney rank sum test or Kruskal-Wallis test was used for continuous variables without a normal distribution in the univariate analysis If a significant difference was found with ANOVA pairwise comparison would be performed with the Scheffe test Multivariate analysis of variance MANOVA was used to identify the most significant factors affecting the cognitive function IQ and the four composite subscales P values less than 005 were considered significant
This study involved 621 EV71 patients in total 534 of them at the CGCH and 87 of them at the NTUH Of these 232 cases 374 had CNS involvement The clinical severity of the EV71 CNS involvement was classified in terms of the increasing severity of the infection Group 1 cases with mild CNS involvement ie aseptic meningitis Group 2 cases with severe CNS involvement including encephalitis polio-like syndrome or encephalomyelitis and Group 3 cases with cardiopulmonary failure after central nervous system involvement Patients placed in Group 1 were those experiencing headaches irritability and CSF pleocytosis 5x106 leukocytesL but no altered level of consciousness or focal signs Patients placed in Group 2 were encephalitis with an altered level of consciousness plus CSF pleocytosis poliomyelitis-like syndrome with acute limb weakness and decreased reflex and muscle strength and encephalomyelitis with the occurrence of both encephalitis and poliomyelitis-like syndrome Patients placed in Group 3 were those who had experienced cardiopulmonary failure defined as a decreased ejection fraction of the left ventricle as assessed by echocardiography with or without pulmonary edemahemorrhage necessitating inotropic agent and ventilator support Patients who experienced cardiopulmonary failure after CNS involvement have been found to have had a sudden onset of cardiopulmonary failure several hours or several days after the manifestations of their EV71 CNS infections516 Of these 232 cases with CNS involvement 25 108 patients died of cardiopulmonary failure and brainstem encephalitis during acute illness 19 of these 25 patients died within 7 days of the onset of acute illness while 14 60 patients died due to a deep coma or aspiration pneumonia during the convalescent stage ie more than one month after onset of their disease
Of the remaining 193 patients with CNS involvement 172 of these at the CGCH and 21 of these at the NTUH 22 refused to be assessed and 29 could not be located This means that a total of 142 736 patients were enrolled in our study and took the assessment between January 2003 and December 2005 after informed consent was obtained from their parents Figure 1 The clinical severity and the demography of the 142 patients who were assessed and the 51 patients who were not assessed p022 for clinical severity p033 for their age of onset and p035 for genders were similar It is therefore clear that the size of the study population involving these 142 patients is representative of the 193 EV71 patients with CNS involvement
Clinical and neurological outcome and neurodevelopment assessment All the children were physically and neurologically examined by a pediatrician or a pediatric neurologist during an outpatient visit or during their stay at chronic respiratory centers Their physical handicap or neurological sequelae the requirement of ventilator support and the need of tube feeding were recorded
EV71 patients who were younger than 6 years of age during our assessment were tested with the Denver Developmental Screening Test DDST II The DDST II has four categories gross motor fine motor language and personal-social17 Each test item was scored as either passed or failed The overall assessment of each child was considered normal when the child passed tasks in 25-75 for hisher age or delayed when the child failed tasks to the left of hisher age line
Cognitive function assessment The Wechsler Intelligence Scale for Children-Third Edition WISC-III Wechsler 1991 profile was individually assessed by a child psychologist for all children over four years of age except for 3 of the children who had tracheostomy and could not talk The WISC-III is a widely used measure of general intelligence for children aged 4-16 years The WISC-III is composed of 13 subtests to test childrens cognitive ability of different dimensions which are grouped into two scores the performance IQ score and the verbal IQ score The Performance IQ score 7 subtests includes Picture Completion Block Design Object Assembly Picture Arrangement Coding Symbol Search and Mazes subtests The Verbal IQ score 6 subtests includes Information Comprehension Arithmetic Similarities Digit Span and Vocabulary subtests18 Four factorially derived composite subscales have been created 1 Verbal Comprehension Information Similarities Vocabulary and Comprehension 2 Perceptual Organization Picture Completion Picture Arrangement Block Design and Object Assembly 3 Freedom From Distractibility Arithmetic and Digit span and 4 Process Speed Coding and Symbol Search 18 Each of the IQ scores and four composite subscales yield standard scores with a mean of 100 and a standard deviation SD of 15
Statistical Analysis Data were analyzed with the SAS Statistical Package Version 91 SAS Institute Cary North Carolina Data are expressed as mean SD median range or number percentage The Chi-square test was used for categorical data and the student t-test and analysis of variance ANOVA were used for continuous variables with normal distribution The Mann-Whitney rank sum test or Kruskal-Wallis test was used for continuous variables without a normal distribution in the univariate analysis If a significant difference was found with ANOVA pairwise comparison would be performed with the Scheffe test Multivariate analysis of variance MANOVA was used to identify the most significant factors affecting the cognitive function IQ and the four composite subscales P values less than 005 were considered significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None