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The purpose of this study was to assess the respiratory muscle strength (RMS) in individuals with mental retardation (MR), with or without Down Syndrome (DS), and its association with bone mineral density (BMD). Forty-five male individuals (15 with DS, 15 with mental retardation (MR) and 15 apparently healthy controls), aged 20-35, participated in this study. Subject assessment included pulmonary function tests, RMS (maximal inspiratory pressure, MIP, and maximal expiratory pressure, MEP) and BMD of the second and fourth lumbar vertebrae. ANOVA was used to test differences amongst groups. Tukey post hoc test was utilized when significant differences were detected with ANOVA. Bivariate correlation for BMD and respiratory muscle strength was calculated with Pearson's coefficient of correlation. Individuals with MR, both with and without DS, have lower FEV1, FVC, MIP and MEP (p<0.001) compared to controls. Individuals with DS also had lower BMD, which was associated with lower MIP and MEP. Hypotonia, sedentary lifestyle and obesity are factors that may explain lower MIP and MEP in DS. Strategies to increase RMS could decrease the risk of osteoporosis in the DS population., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Aim: Assessment of intellectual development of 6-year-old children following asymptomatic or mildly symptomatic congenital cytomegalovirus infection in infancy., Material and Methods: A longitudinal, prospective cohort study concerning 38 (2%) children with congenital cytomegalovirus infection confirmed by specific serological and molecular tests, selected from the group of 1895 neonates preliminarily enrolled into the study. The first specialistic clinical assessment was performed during the neonatal and early infancy period, the second at the age of 12-18 months, and the final comprehensive clinical evaluation was carried out at the age of 6-6.5 years., Results: Psychological evaluation showed normal mental development (Intelligence Quotient ranged from 88 to 114), but 12 (32%) children showed abnormalities in speech development and in 3 (8%) poor visual-motor integration was observed. Emotional and social functioning indicate a normal level of maturity, but 14 (37%) children exhibited increased emotional sensitivity. Psychological assessment indicate that 6 (16%) children may have problems with school maturity., Conclusions: Long-term follow-up of children with congenital cytomegalovirus infection is necessary, including those with a mild clinical course, in view of the possible late sequelae, especially concerning intellectual development and hearing impairment.

Aim: Complete or subtotal absence of one cerebellar hemisphere is exceptional; only single cases have been described. We aimed to assess the long-term outcome in children with severe unilateral cerebellar hypoplasia (UCH)., Method: As part of a retrospective study we describe neuroimaging features, clinical findings, and cognitive outcomes of seven children with UCH (five males, two females; age at first magnetic resonance imaging [MRI]: median 1y 3mo, range 9d-8y 10mo; age at latest follow-up: median 6y 6mo, range 2y 3mo-14y 11mo)., Results: One child had abnormalities on prenatal MRI at 21 weeks' gestation. The left cerebellar hemisphere was affected in five children, and the right hemisphere in two children. The vermis was involved in five children. The volume of the posterior fossa was variable. At the latest follow-up, neurological findings included truncal ataxia and muscular hypotonia in five children, limb ataxia in three patients, and head nodding in two patients. Three children had learning disability*, five had speech and language disorders, and one had a severe behavioural disorder., Interpretation: Severe UCH is a residual change after a disruptive prenatal cerebellar insult, most likely haemorrhagic. The outcome is variable, ranging from almost normal development to marked developmental impairment. Ataxia is a frequent but not a leading sign. It seems that involvement of the cerebellar vermis is often, but not consistently, associated with a poorer cognitive outcome, whereas an intact vermis is associated with normal outcome and no truncal ataxia.

Objective: Aicardi-Goutières syndrome (AGS) is an early-onset encephalopathy resembling congenital viral infection that is characterized by basal ganglia calcifications, loss of white matter, cerebrospinal fluid (CSF) lymphocytosis, and elevated interferon-alpha levels in the CSF. Studies have shown that AGS is an autosomal-recessive disease linked to mutations in 5 genes, encoding the 3'-repair DNA exonuclease 1 (TREX1), the 3 subunits of ribonuclease H2 (RNASEH2A-C), and sterile alpha motif domain and HD domain-containing protein 1 (SAMHD1). In this study we further characterized the phenotypic spectrum of this disease., Methods: Clinical and laboratory data were obtained from 26 patients fulfilling the clinical diagnostic criteria for AGS. Genomic DNA was screened for mutations in all 5 AGS genes by direct sequencing, and sera were analyzed for autoantibodies., Results: In 20 patients with AGS, 20 mutations, 12 of which were novel, were identified in all 5 AGS genes. Clinical and laboratory investigations revealed a high prevalence of features (some not previously described in patients with AGS) that are commonly seen in patients with systemic lupus erythematosus (SLE), such as thrombocytopenia, leukocytopenia, antinuclear antibodies, erythematous lesions, oral ulcers, and arthritis, which were observed in 12 (60%) of 20 patients with AGS. Moreover, the coexistence of AGS and SLE, was for the first time, demonstrated in 2 patients with molecularly proven AGS., Conclusion: These findings expand the phenotypic spectrum of lupus erythematosus in AGS and provide further insight into its disease mechanisms by showing that activation of the innate immune system as a result of inherited defects in nucleic acid metabolism could lead to systemic autoimmunity.

Purpose: To investigate the incidence, risks, severity, and sequelae of posterior fossa syndrome (PFS) in children with medulloblastoma., Methods and Materials: Between 1990 and 2007, 63 children with medulloblastoma at Emory University and Children's Healthcare of Atlanta were treated with craniectomy followed by radiation. Fifty-one patients were assigned to a standard-risk group, and 12 patients were assigned to a high-risk group. Five patients had <1.5-cm(2) residual tumor, 4 had >or=1.5-cm(2) residual tumor, and the remainder had no residual tumor. Eleven patients had disseminated disease. Patients received craniospinal irradiation at a typical dose of 23.4 Gy or 36 Gy for standard- or high-risk disease, respectively. The posterior fossa was given a total dose of 54 or 55.8 Gy. Nearly all patients received chemotherapy following cooperative group protocols., Results: Median follow-up was 7 years. PFS developed in 18 patients (29%). On univariate analysis, brainstem invasion, midline tumor location, younger age, and the absence of radiographic residual tumor were found to be predictors of PFS; the last two variables remained significant on multivariate analysis. From 1990 to 2000 and from 2001 to 2007, the proportions of patients with no radiographic residual tumor were 77% and 94%, respectively. During the same eras, the proportions of patients with PFS were 17% and 39%. Only 4 patients had complete recovery at last follow-up., Conclusions: The incidence of PFS increased in the latter study period and is proportional to more aggressive surgery. Children with midline tumors exhibiting brainstem invasion are at increased risk. With the increased incidence of PFS and the permanent morbidity in many patients, the risks and benefits of complete tumor removal in all patients need to be reexamined.

Aim: Our aim was to study the clinical presentation, mode of diagnosis, and epidemiology of mitochondrial disorders in children from the UK who have progressive intellectual and neurological deterioration (PIND)., Method: Since April 1997, we have identified patients aged 16 years or younger with suspected PIND through the monthly notification card sent to all UK consultant paediatricians by the British Paediatric Surveillance Unit. Clinical details obtained from reporting paediatricians are classified by an Expert Group., Results: By July 2008, 2493 cases of PIND had been reported, among which there were 112 children (69 males, 43 females) with mitochondrial diseases presenting between birth and 14 years 7 months (median 12mo), divided into 13 subgroups. In some instances, clinical features were characteristic of mitochondrial disease, but many children presented non-specifically with combinations of developmental delay, hypotonia, failure to thrive, and seizures; 16 children had multisystem disease at presentation. Mortality was high: 40 children had died. Blood and/or cerebrospinal fluid lactate measurements were abnormal in 87 children, and 47 of 78 brain magnetic resonance images showed increased basal ganglia signal. Definite diagnoses were usually made by muscle enzyme or genetic studies., Interpretation: This is a unique population-based study of the mitochondrial disorders that cause childhood neurodegenerative disease. It provides detailed information about the clinical presentation and investigation of these complex cases.

Objective: We obtained normative data on bruising in children with physical disability in functioning and evaluated factors associated with bruising in this population., Methods: We studied children with physical and/or cognitive disabilities who attend a school that provides comprehensive services. Over a 15-month period, the children had skin examinations, including external inspection of the genitalia and anus. For each child, we gathered information on demographics, medications, growth measures, medical conditions, equipment used, and muscle tone. Functional independence in basic mobility, self-care, and social communication was assessed by using the Functional Independence Measure for Children (WeeFIM). Results were compared with a previously studied nondisabled or "typical" population of children., Results: Fifty children and adolescents 4 to 20 years of age had 2 skin examinations. There was no relationship between the number of bruises and the child's age, race, or BMI. Overall, our subjects were more likely to have at least 1 bruise noted than nondisabled children from a comparable study. There was no significant relationship between the number of bruises and functional mobility, self-care, cognition, or muscle tone. The bruising locations in our study group were different from those of nondisabled children. However, in both groups bruises were rarely found on the neck, ears, chin, anterior chest, or buttocks., Conclusions: The children in our study were different from nondisabled children in the frequency and pattern of their bruising. Areas uncommonly bruised in typical children were also uncommonly bruised in the disabled children. Although increasing age and mobility clearly make a difference in the number of bruises a typically functioning child sustains, these factors are not relevant when evaluating bruises on a child with disabilities. Other factors such as muscle tone, cognition, and equipment should be considered when evaluating a child with significant disabilities who presents with bruises.

Aim: This study is an overview of non-polio enterovirus (NPEV) circulating in North India studied from the perspective of poliomyelitis eradication. Wild polio cases declined because of intensive oral polio vaccine immunization. As we approach global eradication of poliovirus (PV), NPEV causing acute flaccid paralysis (AFP) are equal cause of concern., Methods: A total of 46 653 AFP samples (World Health Organization) and apparently 1000 healthy contacts living in the same geographical area were studied (2004-2007). Serological identification of NPEV was done using RIVM-specific pools (The Netherlands). Untyped (UT)-NPEVs were sequenced directly from reverse transcription-polymerase chain reaction using pan-enterovirus (Pan-EV) primer (CDC, Atlanta, GA) targeting highly conserved 5'un-translated regions of the enterovirus., Results: In this study, 12 513 NPEVs were isolated from the collected stool samples. Seroneutralization had identified 67% of NPEV isolates, whereas 32.6% remained as UT- NPEV. Of the typed NPEVs, Coxsackie-B accounted for 32.3%; followed by echoviruses-11, 12, 13, 7 between 8 and 28%. In sequencing few UT-NPEVs, some were identified also as echovirus-30, 11 and 18 which were probably present in mixtures as they remained UT-NPEV in ENT. Newly classified human enterovirus virus-86 (HEV) (EU079026), HEV-97(EU071767) and HEV-B isolate (EU071768) were isolated in AFP samples., Conclusions: This study provided definitive information about circulation, prevalence and new emerging NPEV in the polio-endemic region of India, hence they should be considered in AFP surveillance. This would help in adopting and planning new strategies in post-PV eradication era in the country. This is the right time to prepare for the future tasks while we head towards a polio-free region.

Objective: Utilizing a population-based registry, the burden of comorbidity was ascertained in a sample of children with cerebral palsy and stratified according to both neurologic subtype and functional capability with respect to gross motor skills., Methods: The Quebec Cerebral Palsy Registry was utilized to identify children over a 4-year birth interval (1999-2002 inclusive) with cerebral palsy. Information on neurologic subtype classified according to the qualitative nature and topographic distribution of the motor impairment on neurologic examination, Gross Motor Function Classification System (GMFCS) categorization of motor skills, and the presence of certain comorbidities (cortical blindness, auditory limitations, nonverbal communication skills, gavage feeding status, and coexisting afebrile seizures in the prior 12 months) was obtained., Results: The frequency of individual comorbidities, their proportional distribution, and mean number of occurrences basically falls into a significant dichotomous distribution. Across the spectrum of comorbidities considered, these comorbidities are relatively infrequently encountered in those with spastic hemiplegic or spastic diplegic variants or ambulatory GMFCS status (levels I-III), while these entities occur at a frequent level for those with spastic quadriplegic, dyskinetic, or ataxic-hypotonic variants or nonambulatory GMFCS status (levels IV and V)., Conclusion: The enhanced burdens of comorbidity are unevenly distributed in children with cerebral palsy in a manner that can be associated with either a specific neurologic subtype (spastic quadriplegic, dyskinetic, ataxic-hypotonic) or nonambulatory motor status (Gross Motor Function Classification System levels IV and V). This provides enhanced value to the utilization of these classification approaches.

Objective: To describe the occurrence of serious bacterial infections (SBIs) in well-appearing, afebrile infants aged 60 days or younger with an apparent life-threatening event (ALTE)., Study Design: We retrospectively reviewed microbiologic testing in a cohort of well-appearing, afebrile infants aged 60 days or younger who presented with an ALTE to a children's hospital emergency department between January 2002 and July 2005. All patients were admitted and followed up for 6 months. Comparisons were made among those who did and did not undergo microbiologic testing and full sepsis evaluation (blood, urine, and cerebrospinal fluid) and those who did and did not have an SBI., Results: Of 182 patients, 112 (61.5%) underwent microbiologic testing, and 53 (29.1%) had a full sepsis evaluation. Five patients (2.7%; 95% confidence interval, 0.9%-6.3%) had an SBI including 3 positive results in blood cultures, 1 positive result in urine culture, and 1 positive result for pertussis by polymerase chain reaction. No patient had a positive result in cerebrospinal fluid culture (95% confidence interval, 0%-5.7%). Patients with a history of prematurity were more likely to have an SBI (6.7% vs. 0.8%, P = 0.04)., Conclusions: Serious bacterial infection occurred in 2.7% of well-appearing, afebrile infants aged 60 days or younger with an ALTE. Prematurity was associated with having an SBI. For premature infants aged 60 days or younger who present with an ALTE, an evaluation for SBI should be strongly considered.

Background: The chromosome 17q21.31 microdeletion syndrome is a novel genomic disorder that has originally been identified using high resolution genome analyses in patients with unexplained mental retardation., Aim: We report the molecular and/or clinical characterisation of 22 individuals with the 17q21.31 microdeletion syndrome., Results: We estimate the prevalence of the syndrome to be 1 in 16,000 and show that it is highly underdiagnosed. Extensive clinical examination reveals that developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour are the most characteristic features. Other clinically important features include epilepsy, heart defects and kidney/urologic anomalies. Using high resolution oligonucleotide arrays we narrow the 17q21.31 critical region to a 424 kb genomic segment (chr17: 41046729-41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau (MAPT). Mutation screening of MAPT in 122 individuals with a phenotype suggestive of 17q21.31 deletion carriers, but who do not carry the recurrent deletion, failed to identify any disease associated variants. In five deletion carriers we identify a <500 bp rearrangement hotspot at the proximal breakpoint contained within an L2 LINE motif and show that in every case examined the parent originating the deletion carries a common 900 kb 17q21.31 inversion polymorphism, indicating that this inversion is a necessary factor for deletion to occur (p<10(-5))., Conclusion: Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.

The objectives of our study were to determine the actual frequency of the different disorders causing neonatal hypotonia and to assess the reliability of the first physical examination as well as the contribution of the main standard diagnostic tests. One hundred and forty-four infants diagnosed with neonatal hypotonia between January 1st 1999 and June 30th 2005 in our tertiary care facility were retrospectively included in the study. Perinatal history, clinical type of hypotonia, results of standard diagnostic tests, final diagnosis and outcome were abstracted from the original charts. A final diagnosis was reached in 120 cases. Central (cerebral) causes represented 82% of the elucidated cases, mostly hypoxic and hemorrhagic lesions of the brain (34%), chromosomal aberrations and syndromic disorders (26%) and brain malformations (12%). Peripheral (neuromuscular) causes were mainly represented by spinal muscular atrophy (6%) and myotonic dystrophy (4%). Positive predictive value of the initial clinical examination was higher in central type hypotonia. Neuroimaging, karyotype analysis and DNA-based tests were the most helpful diagnostic tools. These recent clinical data can be used to improve our strategy in investigating neonatal hypotonia and a diagnostic algorithm is proposed based on our findings.

This study presents a large multicenter cohort of children with cerebral venous thrombosis from 5 centers in the United States and analyzes their clinical findings and risk factors. Seventy patients were included in the study (25 neonates, 35%). The age ranged from 6 days to 12 years. Thirty-eight (55%) were younger than 6 months of age, and 28 (40%) were male. Presenting features included seizures (59%), coma (30%), headache (18%), and motor weakness (21%). Common neurological findings included decreased level of consciousness (50%), papilledema (18%), cranial nerve palsy (33%), hemiparesis (29%), and hypotonia (22%). Predisposing factors were identified in 63 (90%) patients. These included infection (40%), perinatal complications (25%), hypercoagulable/hematological diseases (13%), and various other conditions (10%). Hemorrhagic infarcts occurred in 40% of the patients and hydrocephalus in 10%. Transverse sinus thrombosis was more common (73%) than sagittal sinus thrombosis (35%). Three children underwent thrombolysis, 15 patients received anticoagulation, and 49 (70%) were treated with antibiotics and hydration. Nine (13%) patients (6 of them neonates) died. Twenty-nine patients (41%) were normal, whereas 32 patients (46%) had a neurological deficit at discharge. Seizures and coma at presentation were poor prognostic indicators. In conclusion, cerebral venous thrombosis predominantly affects children younger than age 6 months. Mortality is high (25%) in neonatal cerebral venous thrombosis. Only 18 (25%) patients were treated with anticoagulation or thrombolysis.

The aim of this study was to categorize speech problems in autistic children in a manner allowing recognition of associated risk factors. We were specifically interested in the role of epilepsy and epileptiform activity in EEG in autistic patients since these dynamic processes can influence each other. We combined subtypes of autism with degrees of their functionality and we selected three speech endpoints: i) delayed development of speech, ii) complete mutism and iii) regression of speech. We retrospectively examined 205 autistic children (boys 145/70.7%, mean age 10 years). Median IQ was 55 (15;104) and median Childhood Autism Rating Scale (CARS) ranged within 38 (32;48). Univariate and multivariate logistic regression helped to define clinical and diagnostic factors that were significantly associated with speech endpoints. Epileptic seizures, epileptiform EEG abnormalities, non-right-handedness, hypotonia and severe decreased IQ score were found to be the most important mutually independent factors contributing to the increased risk of speech-related problems in patients with ASD.

Background: The live-attenuated oral polio vaccine used to interrupt poliovirus transmission is genetically unstable. Reversion of some attenuating mutations, which normally occurs during vaccine strain replication in some recipients, and can rarely cause vaccine-associated paralytic poliomyelitis (VAPP). The poliovirus eradication program designed by the World Health Organization (WHO) includes immunization with OPV in addition to careful surveillance of all acute-flaccid paralysis (AFP) cases., Objectives: In Iran we last isolated imported wild poliovirus in 2000 and the immunization coverage was 100% in 2002. During 2001, there were three AFP cases with residual paralysis from which Sabin-like type 1 polioviruses were isolated in our national polio laboratory., Study Design: The complete VP(1) region of the three isolates was sequenced and amino acid substitutions associated with these neurovirulent isolates were recorded., Results: These isolates had either 4, 2 or 1 nucleotide substitution(s) in the VP(1) region, corresponding to amino acid change in the VP(1) of isolate 1 of either (H-[149]->Y), (T-[106]->A) or (I-[90]->L), respectively., Conclusions: Surveillance of the VAPP cases in countries where endemic transmission has recently ceased increases our understanding of the important neurovirulent mutations in vaccine-strain isolates and assists in planning the next step in the eradication program in these countries.

Background: Infants with congenital diaphragmatic hernia require complex surgical care and may have neurodevelopmental morbidity. We examined the performance of reports of motor functioning in 25 congenital diaphragmatic hernia survivors using the parent-completed Developmental Profile-II and a clinical evaluation by a neurodevelopmental pediatrician (MD) measured against the Bayley motor scale., Methods: Bayley motor scores were dichotomized as normal or abnormal. Sensitivity and specificity were calculated for each test., Results: The median age at assessment was 25 months. Bayley motor scores were abnormal in 77% of infants tested (10/13). The MD examinations detected motor problems in 92% (12/13). Sensitivity and specificity of the MD examination were 1.0 and 0.33, respectively. Developmental Profile-II physical scores were abnormal in 15% (2/13); sensitivity and specificity were 0.2 and 1.0, respectively., Conclusions: The high rate of abnormal motor findings in this study supports the need for ongoing screening and evaluation. The sensitivity of MD examinations was excellent, but hypotonia findings were not universally corroborated by the Bayley. Although specificity of parent-reported motor findings was high, parents underreported abnormal motor findings. Parental reports of neurodevelopmental problems should be heeded, and physicians should perform screening motor examinations. Bayley assessments may be warranted to determine the functional implications of observed abnormalities.

One pedigree with four patients has been recently described with mitochondrial DNA depletion and mutation in SUCLA2 gene leading to succinyl-CoA synthase deficiency. Patients had a Leigh-like encephalomyopathy and deafness but besides the presence of lactic acidosis, the profile of urine organic acid was not reported. We have studied 14 patients with mild 'unlabelled' methylmalonic aciduria (MMA) from 11 families. Eight of the families are from the Faroe Islands, having a common ancestor, and three are from southern Italy. Since the reaction catalysed by succinyl-CoA synthase in the tricarboxylic acid (TCA) cycle represents a distal step of the methylmalonic acid pathway, we investigated the SUCLA2 gene as a candidate gene in our patients. Genetic analysis of the gene in the 14 patients confirmed the defect in all patients and led to the identification of three novel mutations (p.Gly118Arg; p.Arg284Cys; c.534 + 1G --> A). The defect could be convincingly shown at the protein level and our data also confirm the previously described mitochondrial DNA depletion. Defects in SUCLA2 can be found at the metabolite level and are defined by mildly elevated methylmalonic acid and C4-dicarboxylic carnitine concentrations in body fluids in association with variable lactic acidosis. Clinically the diagnosis should be considered in patients with early/neonatal onset encephalomyopathy, dystonia, deafness and Leigh-like MRI abnormalities mainly affecting the putamen and the caudate nuclei. The frequency of the mutated allele in the Faroese population amounted to 2%, corresponding with an estimated homozygote frequency of 1 : 2500. Our data extend knowledge on the genetic defects causing MMA. Our patients present with an early infantile Leigh-like encephalomyopathy with deafness, and later on a progressive dystonia. Mild MMA, lactic acidosis and specific abnormalities in the carnitine ester profile are the biochemical hallmarks of the disease. In view of the frequency of the mutated allele on the Faroe Islands, measures become feasible to prevent the occurrence of the disease on the islands. We confirm and extend the findings on this inborn error of metabolism in the TCA cycle that must be carefully investigated by accurate metabolite analyses.

Objective: To review the management and outcome of babies with antenatally diagnosed congenital cystic adenomatoid malformation., Design: Retrospective cohort review., Setting: Tertiary neonatal care unit at Queen Mary Hospital and antenatal diagnostic centre at Tsan Yuk Hospital., Patients: Consecutive patients with antenatally suspected congenital cystic adenomatoid malformation in their concepti among antenatal patients attending Tsan Yuk Hospital from 1994 to 2002. Twenty-four of 33 cases were referred to Queen Mary Hospital for postnatal management and for whom comprehensive records were available for analysis in 23., Interventions: Postnatal interventions in their babies included investigational imaging for congenital cystic adenomatoid malformation and surgery., Main Outcome Measures: Antenatal and postnatal outcome, as well as pathology of the excised lesions., Results: Antenatal outcome: termination of pregnancy in two cases and spontaneous abortion in one; in-utero regression was documented in nine cases and in one hydropic change was apparent. Postnatal outcome: only eight of 20 babies born alive had symptoms in neonatal period. Two developed serious infective complications in infancy, one with documented in-utero regression. Pulmonary parenchymal abnormalities were detected on computed tomography of the thorax in six of seven cases with normal or non-specific chest radiograph findings. Among nine cases with in-utero regression, congenital cystic adenomatoid malformation was confirmed by operative histology in five and abnormal computed tomography findings in three. Fifteen babies underwent surgical excision, one of whom died because of severe pre-existing pulmonary hypoplasia and nine endured minor postoperative complications. A favourable outcome was documented at a mean follow-up of 22 months (range, 2 months-7 years)., Conclusions: In-utero regression of congenital cystic adenomatoid malformation on antenatal ultrasound may not represent genuine resolution. Computed tomographic thorax should be considered in all newborns with antenatally diagnosed congenital cystic adenomatoid malformation, and if confirmed early operation before first hospital discharge is recommended.

Background: Acute flaccid paralysis (AFP) can be caused by a number of conditions. A common preventable cause is poliomyelitis which is still being reported in Pakistan, Guillain Barre Syndrome (GBS), also known as Acute Inflammatory Demyelinating Polyneuropathy, is another common cause of acute flaccid paralysis. It is important to recognize GBS in childhood as parents consider all acute flaccid paralysis to be due to poliomyelitis. The present study was designed to know the frequency of different causes of acute flaccid paralysis in Hazara division., Methods: This is a retrospective analysis of cases of acute flaccid paralysis reported from various districts of Hazara division during the period January 2003 to December 2004. Acute flaccid paralysis was diagnosed clinically through history and clinical examination. The underlying cause of acute flaccid paralysis was investigated by appropriate laboratory tests, such as serum electrolytes, cerebrospinal fluid analysis, electromyogram, nerve conduction study and stool culture for polio virus and other enteroviruses. Diagnosis of Poliomyelitis was confirmed by stool testing for poliovirus., Results: 74 patients presented with AFP during the study period. 36 were male and 38 were female. Guillain Barre syndrome and enteroviral encephalopathy were the two leading causes of acute flaccid paralysis. Majority of the cases were reported from Mansehra district. Children of age groups 12 to 24 months and > 96 months constituted the majority (20% each)., Conclusion: Guillian Barre syndrome was the leading cause of acute flaccid paralysis reported from various parts of Hazara division.

We reviewed collapse (sudden onset of pallor, limpness and hyporesponsiveness) following the first infant (DPTP+Hib) vaccination reported to the enhanced passive surveillance system of the Netherlands in 1994-2003. All 1303 reports identified by the current RIVM (National Institute for Public Health and Environment) case definition were captured by the Brighton Collaboration (BC) case definition, with in 17 (1.3%) reports insufficient information. Over the years the proportion of the highest level of diagnostic certainty (level 1) increased due to more complete data from 70% to over 90%. We checked the BC case definition also on a sample of cases (with pallor or hyporesponsiveness) not meeting RIVM's case definition for collapse at the time. Sixty out of 200 cases were captured by BC but again rejected by RIVM. The sensitivity BC levels 2 and 3 appeared too high. We recommend a more restrict case definition by the Brighton Collaboration with certain exclusion criteria to make it more specific. Furthermore a change in the specifications for levels 2 and 3 will increase specificity and accommodate for the loss of sensitivity.

Study Objective: To determine the frequency of rapid eye movement (REM) sleep behavior disorder (RBD) and REM sleep without atonia among patients with Alzheimer disease and control subjects., Design: Overnight polysomnography., Settings: Sleep laboratory., Patients: Fifteen patients with probable Alzheimer disease (mean age +/-SD, 70.2+/-5.6) and 15 age-matched healthy control subjects (mean age +/- SD, 67.9 +/-5.4)., Intervention: N/A., Results: Four patients with Alzheimer disease presented REM sleep with-out atonia. One of these patients had all the polysomnographic features of RBD, including behavioral manifestations during REM sleep., Conclusion: RBD is rare, but REM sleep without atonia is relatively fre-quent in patients with probable Alzheimer disease, a tauopathy.

In this preliminary study, it was examined whether capacity to react to external stress (acute pain) during neonatal intensive care predicts later neuromotor development at 4 and 8 months corrected chronological age (CCA) in high-risk preterm infants. Behavioural and cardiac reactivity to blood collection at 32 weeks postconceptional age (PCA) were recorded in addition to developmental outcomes at 4 and 8 months CCA in 35 preterm infants (17 males, 18 females) born

Objectives: The objective of this review was to assess the efficacy of episiotomy to prevent severe perineal tears, urinary incontinence, faecal incontinence and genital prolapse., Material and Methods: A systematic review on Medline database was performed between 1980 and 2005. One hundred seventy seven articles were selected. Trial quality was assessed on the following parameters: design (prospective, randomized, meta-analysis), sample size (>50) and relevant results. Finally, 43 articles were analysed., Results: The routine use of episiotomy did not prevent severe perineal tears. It decreased the risk of moderate anterior perineal lacerations. The risk of severe perineal tears during episiotomy increased in the following circumstances: primiparity, Asian women, perineal length

Background: Since hypotonia is the phenotype of several clinical conditions that do not always lead to a favorable outcome, prompt diagnosis is important. Congenital Hypotonia with Favorable Outcome (CHFO), an underestimated condition, should be rapidly differentiated from other more serious hypotonic states by means of simple, effective and only slightly invasive instrumental diagnostic examinations., Aim: We analyzed the electromyographic data of a group of patients with CHFO and compared them with data taken from their muscle biopsies to evidence the utility of the electromyographic study (EMG) in this condition., Methods: We performed EMG, nerve conduction study (NCS) and muscle biopsy on 41 subjects with a diagnosis of CHFO (age range 9 months to 12 years, mean age, 6.7 years)., Results: No specific EMG findings were observed. Muscle biopsy was normal in all subjects, and we obtained concordance between biopsy and EMG in 85% of the subjects (35/41)., Conclusion: A normal EMG examination helps investigators to exclude several neurological diseases characterized by hypotonia and it can provide valuable complementary information to confirm the clinical diagnosis of CHFO.

Obstructive sleep apnea (OSA) syndrome is a common disorder among children and is often associated with significant morbidity. The causes of OSA are related to either fixed upper airway abnormalities such as adenotonsillar hypertrophy, or dynamic airway abnormalities such as laryngomalacia and pharyngeal wall collapse. The aim of the present study was to determine the prevalence of dynamic upper airway abnormalities, based on endoscopic findings, in normotonic and hypotonic children with polysomnographically documented OSA. The records of 39 consecutive children with OSA who underwent bronchoscopy (22 with normal tone, and 17 with hypotonia) were reviewed. The prevalence of dynamic defects among children with normal tone decreased with age. All 7 patients less than 1 year old had dynamic abnormalities (isolated or combined fixed/dynamic), compared to only 66% (6/9) of patients between 1-2 years old, and 17% (1/6) of children more than 2 years old. In contrast, dynamic abnormalities were very common among hypotonic children, independent of age. Since children with dynamic defects are less likely to respond to surgical treatments, it would be appropriate to identify these children prior to any intervention. Due to the higher frequency of dynamic defects in both infants (< 1 year) and hypotonic children, it may be appropriate to include endoscopy as part of the diagnostic evaluation of OSA in these subgroups., (Copyright 2005 Wiley-Liss, Inc.)

We used acute flaccid paralysis surveillance data collected between 1 January 2001 and 31 December 2003 from the Pakistan Polio Eradication Initiative to describe the epidemiological characteristics and disease burden of traumatic injection neuropathy among children aged under 15 years. Of the 5627 acute flaccid paralysis cases reported, 456 were identified as traumatic injection neuropathy by case review. The condition was more common in younger children who were also more likely to have persistent paralysis. We estimate that the annual incidence of traumatic injection neuropathy rate in Pakistan is 7.1 per 1 000 000 in children under 3 years old.

In many countries, the Enterovirus 71 (EV-71) Picornaviridae family is associated to hand, foot and mouth disease in addition to acute neurological diseases while in Brazil these viruses are more closely associated to the latter group. The aim of this research was to use the first EV-71 isolate of the Northern region of Brazil in molecular and seroepidemiologic studies. Two (2.2%) out of 88 stool samples (44 cases of AFP), collected from January 1998 to December 2000 were positive for EV-71 isolation (73442/PA/99). Nucleotide sequence of the gen that codifies the VP1 protein showed that isolate 73442/PA/99 was similar to the EV-71 strains belonging to genotype B - more closely identified with EV-71 from North America. Neutralization test with 389 sera samples collected from January 1998 to November 2001, from individuals ranging from 0 to 15 years of age living in the city of Belém, State of Para showed the following results in relation to isolate 73442/PA/99 and prototype BrCr: a total of 207 individuals (53.2%) had neutralization antibodies to both viruses, 167 (42.9%) had no antibodies and 15 showed the presence of neutralizing antibodies to one of the two viruses. Only 20.2% of the children aged 0 to 3 had neutralizing antibodies to EV-71, indicating that these children were more susceptible to the infection. Both the seroprevalence study and VP1 sequencing were important to demonstrate the spread and the molecular pattern of the EV-71 circulating in the Northern Region of Brazil.

Cardiointervalometry was used to investigate functional parameters of the cardiorespiratory system during text reading. A total of healthy women aged from 17 to 28 years and 11 women with hypotonic dysphonia 17 to 31 years of age entered the study. Both groups exhibited a low index of parasympathetic component of cardiorhythm regulation in shortening of the RR-interval. Correlation inhalation/expiration has changed with prolongation of inhalation and shortening of expiration in reading in women suffering from hypotonic dysphonia. Parameters of the respiratory cycle at rest did not correlate with relevant parameters in reading text in both groups.

Pharyngeal wall inspiratory collapse (PWIC) is a dynamic obstruction of the air column proximal to the glottis during inspiration. Our objectives were to assess PWIC's incidence and its contribution to the symptoms of upper airway obstruction (UAO), and to propose indications for intervention. In a retrospective review of consecutive endoscopic evaluations and clinical data of 108 infants with UAO, PWIC was diagnosed in 50 infants (46%). The most common presenting symptom was apnea (52%). The PWIC was accompanied by 2 to 7 synchronous airway abnormalities, most frequently laryngomalacia (78%). Generalized hypotonia was the most common associated systemic finding (80%). Severe PWIC cases required bi-level positive airway pressure (BiPAP). The severity of PWIC, measured by a newly developed classification, was positively correlated to apnea (p < .05) and the need for BiPAP (p < .054). Spontaneous recovery occurred within 36 months. The incidence of PWIC among infants with UAO is high, and its role in UAO deserves greater recognition. Better diagnosis of PWIC will improve the treatment of UAO.

The combined vaccine against diphtheria, tetanus and pertussis containing the whole cell component of pertussis (DPTw) is characterized by high effectiveness but is also one of the most reactogenic vaccines. Adverse events following this vaccine includes a hypotonic-hyporesponsive episode, however this episode is not well known to general practitioners and pediatricians, so the data about its incidence are not reliable. The aim of this study was to characterize the clinical features of HHE following DTPw vaccine, to estimate the ability to diagnose this syndrome by GPs and pediatricians and to assess the registration system of HHE in Poland. The studied group consisted of 49 children, patients of the Regional Consultation Polyclinic in Kraków in the years 1997-2002, in whom HHE was diagnosed. The following were analysed: sex and age, interval between vaccination and HHE, relationship to the number of DTPw doses, duration of HHE and, based on the referral, the diagnosis made by a GP. The average age of children at the moment of HHE was 3.4 months, but 46/49 children were under 6 months. The symptoms of HHE occurred after a few minutes to 48 hours after vaccination and in two children similar episodes were observed on the 6th day after vaccination, which is not consistent with the definition of HHE. Most often HHE was observed after the first (21/49) and the second (16/49) dose of DTPw. In two children HHE occurred twice, after two consecutive doses of DTPw. In four cases only GPs referring patients have diagnosed HHE. Thirty children from the studied group were further vaccinated against diphtheria, tetanus and pertussis. 61 doses of DTPa (a vaccine with acellular pertussis component) were used and in no case was the adverse event observed. Based on the results obtained it has been concluded that some difficulties are observed in the diagnosis of HHE made by GPs and pediatricians, therefore the number of HHE cases registered in Poland decreased. Hypotonic-hyporesponsive episode should be taken into consideration in differential diagnosis of the nervous system diseases. Therefore, it is extremely important to ask parents about the history of vaccinations in their children.

The objective of this study was to investigate the incidence of acute flaccid paralysis in the pediatric population of Honduras over an 11-year period, determine what percentage of acute flaccid paralysis was Guillain-Barré syndrome, and identify the epidemiologic features of Guillain-Barré syndrome. There were 546 childhood cases of acute flaccid paralysis seen between January 1989 and December 1999 at the Hospital Escuela Materno-Infantil in Tegucigalpa, Honduras. Of these cases with acute flaccid paralysis, 394 (72.2%) were diagnosed with Guillain-Barré syndrome. Our incidence of Guillain-Barré syndrome in the Honduran pediatric population (1.37/100,000 per year) is higher than that shown in other studies. There was a significantly higher incidence of Guillain-Barré syndrome in younger children (ages 1-4 years), a significant preponderance of cases from rural areas, and a mild predominance in boys but a typical clinical presentation. The Honduran pediatric Guillain-Barré syndrome population had an increased mortality rate. Guillain-Barré syndrome has become the leading cause of childhood paralysis in Honduras. A better understanding of the population at highest risk and opportunities for earlier intervention with more effective therapeutic modalities may permit reducing the mortality among Honduran children who develop Guillain-Barré syndrome.

Objective: Acellular pertussis vaccines were introduced with the promise of an improved safety profile compared with whole-cell vaccines. In 1997-1998, Canada adopted 1 combination acellular pertussis vaccine, having previously used 1 particular combination whole-cell pertussis vaccine. We hypothesized that the change would result in a decrease in hospitalization rates for seizures and reports of hypotonic-hyporesponsive episodes (HHEs) temporally related to pertussis vaccination., Methods: Active surveillance was performed between 1995 and 2001 by the Immunization Monitoring Program-Active monitors at 12 hospitals using standard case definitions. Seizures had to occur within 72 hours after immunization with a pertussis-containing vaccine or 5 to 30 days after immunization with measles-mumps-rubella vaccine. HHE episodes had to occur within 48 hours of receipt of a pertussis-containing vaccine. Poisson regression models were used to compare the average number of monthly admissions for seizures and HHEs before and after introduction of the acellular pertussis vaccine., Results: We found a 79% decrease in febrile seizures associated with receipt of pertussis vaccine but no significant decrease in febrile seizures temporally related to measles-mumps-rubella between 1995-1996 and 1998-2001. There was a 60% to 67% reduction in HHEs associated with pertussis-containing vaccines between the same time periods, depending on case definition., Conclusions: The risks of febrile seizures and HHEs after pertussis-containing vaccine declined significantly with the introduction of acellular pertussis vaccine in Canada. Active surveillance systems are important for detecting trends in uncommon adverse events after routine immunizations.

In Canada since 1993 the nation's passive system for reporting postimmunization adverse events has been supplemented by the active surveillance of inpatients at 10 to 12 pediatric referral centers, a system referred to as the Immunization Monitoring Program, Active. Participating centers are located from coast-to-coast and receive referrals from every province and territory. Approximately 20 percent of the population aged 0 to 12 years lives in the immediate vicinity of these centers. Nurse monitors at each center search for numerous target conditions, including postimmunization adverse events and vaccine-preventable infections. Vaccine safety observations have included (1) a substantial decrease in the risk of the development of febrile seizures and hypotonic-hyporesponsive episodes since the country switched from whole-cell to acellular pertussis-containing vaccines, (2) no evidence for encephalopathy resulting from the latter vaccines, (3) a generally benign outcome with postimmunization thrombocytopenia cases, and (4) an unexpectedly high rate of disseminated bacille Calmette-Guérin infections among aboriginal infants. Concomitant disease surveillance has been important for sustaining the surveillance system because few postimmunization adverse events require hospital admission.

Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (OMIM 218000) is an autosomal recessive disease of early onset characterized by a delay in developmental milestones, a severe sensory-motor polyneuropathy with areflexia, a variable degree of agenesis of the corpus callosum, amyotrophy, hypotonia, and cognitive impairment. Although this disorder has rarely been reported worldwide, it has a high prevalence in the Saguenay-Lac-St-Jean region of the province of Quebec (Canada) predominantly because of a founder effect. The gene defect responsible for this disorder recently has been identified, and it is a protein-truncating mutation in the SLC12A6 gene, which codes for a cotransporter protein known as KCC3. Herein, we provide the first extensive review of this disorder, covering epidemiological, clinical, and molecular genetic studies.

Since the World Health Assembly resolved in May 1988 to eradicate poliomyelitis, the estimated global incidence of polio has decreased >99%, and three World Health Organization (WHO) regions (Americas, Western Pacific, and European) have been certified as polio-free. In 1995, India began accelerating polio eradication activities. By 2001, poliovirus circulation had been limited largely to the two northern states of Uttar Pradesh (UP) and Bihar, with 268 cases reported nationwide. However, in 2002, a major regional resurgence of polio occurred. As of January 25, 2003, a total of 1,556 cases were detected nationwide, of which 1,337 (86%) were in UP and Bihar. This report summarizes the status of polio eradication activities in India during 2002, analyzes the factors contributing to the resurgence, and describes the actions being taken to reduce poliovirus transmission.

Objective: To estimate the incidence and the completeness of ascertainment of acute flaccid paralysis (AFP) in Victoria, Australia, in 1998-2000 and to determine its common causes among children aged under 15 years., Methods: : The two-source capture-recapture method was used to estimate the incidence of cases of AFP and to evaluate case ascertainment in the routine surveillance system. The primary and secondary data sources were notifications from this system and inpatient hospital records, respectively., Findings: The routine surveillance system indicated that there were 14 cases and the hospital record review identified 19 additional cases. According to the two-source capture-recapture method, there would have been 40 cases during this period (95% confidence interval (CI) = 29-51), representing an average annual incidence of 1.4 per 100000 children aged under 15 years (95% CI = 1.1- 1.7). Thus case ascertainment based on routine surveillance was estimated to be 35% complete. Guillain-Barré syndrome was the commonest single cause of AFP., Conclusions: Routine surveillance for AFP in Victoria was insensitive. A literature review indicated that the capture-recapture estimates obtained in this study were plausible. The present results help to define a target notification rate for surveillance in settings where poliomyelitis is not endemic.

In the past decade, the Sultanate of Oman has experienced three outbreaks of paralytic poliomyelitis--a widespread polio type 1 epidemic in 1988/1989, four cases of polio type 3 in three different regions in 1991, and a localized type 1 outbreak in 1993. The lessons learnt from each of these epidemics have guided us to modify and improve our polio eradication activities. Currently, these activities include administration of five primary and three booster doses of trivalent oral polio vaccine, yearly national immunization campaigns (NIDs) since 1995 with coverage of >90%, localized immunization campaigns, acute flaccid paralysis (AFP) surveillance which involves reporting of all cases by facsimile to the Department of Surveillance within 24 h of detecting a case and weekly zero reporting from 22 sentinel sites, and virological testing of stool specimens of all AFP cases and their close contacts at the national, World Health Organization accredited laboratory. The cumulative success of these activities has resulted in Oman being free from polio for the past 6 years. However, the possibility of importation of wild poliovirus, particularly from southern and western Asia still exists.

Dissociated motor development (DMD) is considered when the baby starts independent walking late, with normality of the other fields of development. There is evidence that babies with DMD present an atypical crawling pattern and hypotonia. To investigate the frequency and characteristics of DMD, neurological examination was performed monthly in 177 healthy full-term babies from 6 months age, in urban and rural zone samples in Brazil. Among 20 children with atypical crawling, none presented hypotonia neither did they start independent walking late. The means of the ages at the beginning of atypical crawling and independent walking acquisitions, 7.40 mo (SD 1.4) and 12.76 mo (SD 2.5) respectively, did not differ from the group with crossed crawling pattern. Thus, in this sample of Brazilian healthy children we did not find cases with DMD.

The profile of disorders presenting with neonatal hypotonia to the neonatal intensive care unit has not been studied previously. An 11-year retrospective cohort study of neonates, who were identified through computer database records and were admitted to the Neonatal Intensive Care Unit from January 1989 to December 1999 at the Montreal Children's Hospital (Montreal, Québec), is presented. The final diagnoses, tests obtained, and outcome were determined from a structured review of the subject's hospital record. The database search generated 95 records, of which 50 neonates met the inclusion criteria. The hypotonia was classified as central in 33 patients (66%) and peripheral in 17 (34%). Hypoxic-ischemic encephalopathy (n = 13), Prader-Willi syndrome (n = 6), myotonic dystrophy (n = 6), other muscle disorders (n = 6), chromosomal disorders (n = 4), and peripheral nerve disorders (n = 3) were the most common diagnoses. The genetic tests of highest yield were fluorescent in situ hybridization for Prader-Willi syndrome, DNA methylation studies for Prader-Willi syndrome, trinucleotide repeat testing for myotonic dystrophy, and karyotype analysis. A diagnostic approach is proposed based on the results.

The aim of this study was to describe fieldwork to erradicate poliomyelitis from Afghanistan and particularly from the Mazar Region. From 1997-1999, 365 cases of acute flaccid paralysis were detected. Of these, 216 cases (59.2%) were classified as poliomyelitis. The rate of acute flaccid paralysis improved from 0.1 in 1997 to 0.8 in 1999. Fieldwork in the Mazar region revealed under-notification and the need to improve surveillance methods. However, massive use of the services of traditional healers and extreme transport difficulties reduced the efficacy of the interventions. The case of Afghanistan suggests that epidemiological surveillance systems are feasible in countries with armed conflict, although such systems require considerable resources.

Objective: On 29 October 2000 poliomyelitis was officially declared to have been eradicated from the Western Pacific Region. This article describes the results of surveillance for cases of acute flaccid paralysis (AFP) in China during the final phase of the eradication effort., Methods: We conducted hospital-based active surveillance in high-risk areas for poliomyelitis in 5 provinces of southern-China (Sichuan, Yunnan, Guizhou, Guangxi and Jiangxi) between 1995 and 1997 to determine the adequacy of reporting and laboratory diagnosis of cases of AFP., Findings: A total of 1069 AFP cases occurring since 1993 were identified in 311 hospital visits. Less than 50% of AFP cases occurring in 1993 and 1994 had been reported by AFP surveillance, and laboratory diagnosis had been carried out on only a small proportion of these. However, improved cooperation between hospital sectors increased the rate of case reporting and laboratory diagnosis to 85% and 78%, respectively, in 1997. Despite this overall improvement, these two indicators were approximately 10-20% lower in Yunnan Province. Epidemiological analysis revealed that cases of clinical poliomyelitis accounted for as much as one-third of all AFP in 1993 and that some of these cases were clustered. Clusters were rarely observed after 1994. Active surveillance in the China-Myanmar border areas of Yunnan over 1995-96 detected 9 cross-border cases of clinical poliomyelitis, including 2 of wild poliomyelitis. Import of poliomyelitis was thus considered to have occurred frequently until 1996 in this border area of Yunnan. These data were important for the outbreak response immunization carried out in 1996 in the border prefectures of Yunnan., Conclusion: Our investigation confirmed a high level of AFP surveillance in poliomyelitis high-risk areas of the five provinces and provided valuable information on the interruption of wild poliovirus circulation in southern China that will be of use to countries in other regions that have yet to eradicate poliomyelitis.

After the successful eradication of small pox, the eradication of poliomyelitis was planned. In the poliomyelitis eradication programme, conducted since 1989, routine vaccination, supplemental immunisation activities and acute flaccid paralysis (AFP) surveillance were the main strategies. In 1997, in Mardin provinces six poliomyelitis cases were reported. Therefore it was planned to strengthen the eradication programme in this province and those around it. In 1998 in Mardin and five neighboring provinces, a study was conducted that included monthly visits, educational activities, etc. At the result of this study, 64 AFP cases (22 of them poliomyelitis) were reported. Non-poliomyelitis AFP rate had increased from 0.9 in 1997 to 2.8 in 1998. An adequate two specimen ratio was 72%. We recognised that more poliomyelitis cases were reported in hot seasons when compared with non-poliomyelitis cases reported throughout the year. This difference was statistically significant (P<0.001). Most AFP cases were aged under 35 months. At the 60th day follow-up visits of the patients, we found 90.9% of the poliomyelitis cases but only 19.0% of the non-poliomyelitis case had residual paralysis. Presence of prodromal fever was another finding that distinguished poliomyelitis cases from non-poliomyelitis AFP cases. 90.9% of the poliomyelitis cases but only 64.3% of the non-poliomyelitis cases had fever at onset. This finding was also statistically significant (P<0.05).