Diagnostic performance of automated, streamlined, daily updated exome analysis in patients with neurodevelopmental delay.

BACKGROUND: The diagnostic yield of whole-exome sequencing (WES) varies from 30%-50% among patients with mild to severe neurodevelopmental delay (NDD)/intellectual disability (ID). Routine retrospective reanalysis of undiagnosed patients has increased the total diagnostic yield by 10-15%. Here, we performed proband-only WES of 1065 patients with NDD/ID and applied a prospective, daily reanalysis automated pipeline to patients without clinically significant variants to facilitate diagnoses. METHODS: The study included 1065 consecutive patients from 1056 nonconsanguineous unrelated families from 10 multimedical centers in South Korea between April 2018 and August 2021. WES data were analyzed daily using automatically updated databases with variant classification and symptom similarity scoring systems. RESULTS: At the initial analysis, 402 patients from 1056 unrelated families (38.0%, 402/1,056 families) had a positive genetic diagnosis. Daily prospective, automated reanalysis resulted in the identification of 34 additional diagnostic variants in 31 patients (3%), which increased our molecular diagnostic yield to 41% (433/1056 families). Among these 31 patients, 26 were diagnosed with 23 different diseases that were newly discovered after 2019. The time interval between the first analysis and the molecular diagnosis by reanalysis was 1.2 ± 0.9 years, which was shorter in the patients enrolled during the latter part of the study period. CONCLUSION: Daily updated databases and reanalysis systems enhance the diagnostic performance in patients with NDD/ID, contributing to the rapid diagnosis of undiagnosed patients by applying the latest molecular genetic information.

Characteristics in Pediatric Patients with Coronavirus Disease 2019 in Korea.

BACKGROUND: Based on the reports of low prevalence and severity of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, the Korean government has released new SARS-CoV-2 infection response and treatment guidelines for children under the age of 12 years. The government has further directed school reopening under strict preventive measures. However, there is still considerable concern on the impact of school reopening on community transmission of Coronavirus disease 2019 (COVID-19). In the present study, we aimed to evaluate the appropriateness of these directives and the severity of SARS-CoV-2 infections in children as compared to adults using sufficient national sample data. METHODS: In the present study, we evaluated the severity of SARS-CoV-2 infection in pediatric patients as compared to adults by analyzing the length of hospital stays (LOS), medical expenses, and hospital and intensive care unit (ICU) admission rates. A multivariate linear regression analysis was carried out to examine the effects of COVID-19 patients that the characteristics on the LOS and medical expenses, and multivariate logistic regression analysis were performed to identify COVID-19 characteristics that affect hospital and ICU admission rates and to prove the low SARS-CoV-2 infection severity in pediatric patients. RESULTS: The hospitalization period for children aged 0-9 was 37% shorter and that of patients aged 10-19 years was 31% shorter than those of older age groups (P < 0.001). The analysis of the medical expenses by age showed that on average, medical expenses for children were approximately 4,900 USD lower for children than for patients over 80 years of age. The linear regression analysis also showed that patients who were 0-9 years old spent 87% and those aged 10-19 118% less on medical expenses than those aged 70 and over, even after the correction of other variables (P < 0.001). The probability of hospitalization was the lowest at 10-19 years old (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.03-0.09), and their ICU admission rate was also the lowest at 0.14 (OR, 0.14; 95% CI, 0.08-0.24). On the other hand, the likelihood of hospitalization and ICU admission was the highest in children aged 0-9 years, and among patients under the age of 50 years in general. CONCLUSION: This study demonstrated the low severity of SARS-CoV-2 infection in younger patients (0-19 years) by analyzing the LOS, medical expenses, hospital, and intensive care unit admission rates as outcome variables. As the possibility to develop severe infection of coronavirus at the age of 10-19 was the lowest, a mitigation policy is also required for middle and high school students. In addition, children with underlying diseases need to be protected from high-risk infection environments.

Risk Factors of Outcomes of COVID-19 Patients in Korea: Focus on Early Symptoms.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread around the globe, and it is important to determine the risk factors of death in the general population. Our study aimed to determine the risk factors of death and severe illness requiring supplemental oxygen therapy based on the demographic and clinical characteristics of COVID-19 patients in Korea. METHODS: In this study, we used data provided by the Korea Disease Control and Prevention Agency (KDCA) and analyzed a total of 5,068 patients with COVID-19, excluding 19 pregnant women and 544 individuals with missing data. We performed logistic regression analysis to determine the impact of early symptoms on survival and severe disease. Logistic regression models included sex, age, number of comorbidities, symptoms on admission, blood pressure, heart rate, and body temperature as explanatory variables, and death and oxygen therapy as outcome variables. RESULTS: Logistic regression analyses revealed that the male sex, older age (≥ 60 years), higher number of comorbidities, presence of symptoms on admission, heart rate ≥ 120 bpm, and body temperature ≥ 37.5°C presented with higher risk of in-hospital death and oxygen therapy requirement. Conversely, rhinorrhea and headache were associated with a low risk of death and oxygen therapy requirement. The findings showed that cough, sputum, and fever were the most common symptoms on admission, while 25.3% of patients with COVID-19 were asymptomatic. CONCLUSION: COVID-19 patients with high-risk early symptoms on admission, such as dyspnea and altered mental status, and those without low-risk symptoms of rhinorrhea and headache should be included in priority treatment groups.

Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system, EVIDENCE.

EVIDENCE, an automated variant prioritization system, has been developed to facilitate whole exome sequencing analyses. This study investigated the diagnostic yield of EVIDENCE in patients with suspected genetic disorders. DNA from 330 probands (age range, 0-68 years) with suspected genetic disorders were subjected to whole exome sequencing. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments. EVIDENCE reported a total 228 variants in 200 (60.6%) of the 330 probands. The average number of organs involved per patient was 4.5 ± 5.0. After clinical reassessment and/or family member testing, 167 variants were identified in 141 probands (42.7%), including 105 novel variants. These variants were confirmed as being responsible for 121 genetic disorders. A total of 103 (61.7%) of the 167 variants in 95 patients were classified as pathogenic or probably to be pathogenic before, and 161 (96.4%) variants in 137 patients (41.5%) after, clinical assessment and/or family member testing. Factor associated with a variant being regarded as causative includes similar symptom scores of a gene variant to the phenotype of the patient. This new, automated variant interpretation system facilitated the diagnosis of various genetic diseases with a 42.7% diagnostic yield.

Risk of low serum levels of ionized magnesium in children with febrile seizure.

BACKGROUND: Suboptimal intake of magnesium become prevalent due to the modern diet of processed food low in magnesium. Magnesium may modulate seizure activity by antagonizing excitatory calcium influx through the N-methyl-D-aspartate receptor. Although hyponatremia has been reported to be common in febrile seizures, the most common form of seizure, little is known about the status of serum ionized magnesium. We therefore investigated the status of serum ionized magnesium (iMg2+) in children with febrile seizures and compared with controls. METHODS: We included all patients from 1 to 6 years old who had presented with febrile seizure to the pediatric emergency department at the Korea University Guro Hospital from July 2016 to February 2017. The control group comprised patients admitted to the hospital with febrile respiratory tract infections, but with no history of febrile seizure. Clinical data, blood tests, and electroencephalogram (EEG) results were reviewed using the patients' medical records. RESULTS: A total of 133 patients with febrile seizure and 141 control patients were analyzed in the present study. As a result, hypomagnesemia (< 0.50 mmol/L) was more common in patients with febrile seizure than in controls (42.9% vs. 6.9%, p < 0.001) and it was an independent risk factor for febrile seizure (OR, odds ratio = 22.12, 95% CI = 9.23-53.02, P < 0.001). A receiver operating curve analysis revealed that serum iMg2+ levels < 0.51 mmol/L predicted the presence of febrile seizures with a sensitivity of 45.1% and a specificity of 92.6% (AUC, area under the curve = 0.731, 95% confidence interval = 0.671-0.791). When the patients with febrile seizure were divided in terms of a serum iMg2+ concentration of 0.51 mmol/L, there was no difference in clinical features. CONCLUSIONS: Hypomagnesemia was more common and serum iMg2+ level was lower in patients with febrile seizures than in controls. However, further evidence is needed for the causal relationship between low magnesium and febrile convulsions.

Need for Lumbar Puncture in Children Younger Than 12 Months Presenting With Simple Febrile Seizure.

OBJECTIVES: Recently, conflicting results have been reported regarding the necessity of routine lumbar puncture in children less than 12 months of age with simple febrile seizure. The aims of this study were to evaluate the results of lumbar puncture in children younger than 60 months of age with febrile seizure and to reassess the need for lumbar puncture in children younger than 12 months with simple febrile seizure. METHODS: A retrospective chart review was performed in patients younger than 60 months who presented with febrile seizure and underwent lumbar puncture from January 2005 to January 2015. RESULTS: A total of 1249 patients presenting with febrile seizure were admitted. Of these, 816 met inclusion criteria for presenting with simple febrile seizure. Lumbar puncture was performed in 75 patients (9.2%; age, mean ± SD, 12.05 ± 9.13 months; male/female, 31/44), who were reviewed. Sixty-six (88.0%) of 75 patients were younger than 12 months. Five patients (6.7%) showed pleocytosis in cerebrospinal fluid, and 4 of them were younger than 1 year of age. Three patients (4.0%) had bacterial meningitis and were 4, 8, and 12 months. Streptococcus pneumoniae (2 patients) and Klebsiella pneumoniae (1 patient) were isolated in cerebrospinal fluid. Nobody had neurologic signs suggesting bacterial meningitis, and all of them completed scheduled immunizations and were up-to-date. CONCLUSION: Lumbar puncture should be considered in every child younger than 12 months of age with a simple febrile seizure owing to lack of abnormal neurologic sign even if immunization is up-to-date.

A start codon CMT1X mutation associated with transient encephalomyelitis causes complete loss of Cx32.

X-linked Charcot-Marie-Tooth disease (CMTX1) results from numerous mutations in the GJB1 gene encoding the gap junction protein connexin32 (Cx32) and is one of the commonest forms of inherited neuropathy. Owing to the expression of Cx32 not only in Schwann cells but also in oligodendrocytes, a subset of CMT1X patients develops central nervous system (CNS) clinical manifestations in addition to peripheral neuropathy. While most GJB1 mutations appear to cause peripheral neuropathy through loss of Cx32 function, the cellular mechanisms underlying the CNS manifestations remain controversial. A novel start codon GJB1 mutation (p.Met1Ile) has been found in a CMT1X patient presenting with recurrent episodes of transient encephalomyelitis without apparent signs of peripheral neuropathy. In order to clarify the functional consequences of this mutation, we examined the cellular expression of two different constructs cloned from genomic DNA including the mutated start codon. None of the cloned constructs resulted in detectable expression of Cx32 by immunocytochemistry or immunoblot, although mRNA was produced at normal levels. Furthermore, co-expression with the other major oligodendrocyte connexin, Cx47, had no negative effect on GJ formation by Cx47. Finally, lysosomal and proteasomal inhibition in cells expressing the start codon mutant constructs failed to recover any detection of Cx32 as a result of impaired protein degradation. Our results indicate that the Cx32 start codon mutation is equivalent to a complete loss of the protein with failure of translation, although transcription is not impaired. Thus, complete loss of Cx32 function is sufficient to produce CNS dysfunction with clinical manifestations.

Epilepsy-related clinical factors and psychosocial functions in pediatric epilepsy.

PURPOSE: The aim of this study was to identify the different influencing patterns of demographic and epilepsy-related variables on various aspects of psychosocial function in pediatric epilepsy. METHOD: Five hundred ninety-eight patients with pediatric epilepsy between the ages of 4 and 18 years (boys=360, 60% and girls=238, 40%) and their parents participated in the study. Parents completed the Social Maturity Scale (SMS), the Korean version of the Child Behavior Checklist (K-CBCL), and the Korean version of the Quality of Life in Childhood Epilepsy Questionnaire (K-QOLCE) to assess daily living function, behavior, and quality of life. The Children's Global Assessment Scale (CGAS) was completed by clinicians to assess general adaptive function. Demographic variables, such as age and sex of child, and epilepsy-related clinical variables, including seizure type, seizure frequency, duration of epilepsy, and number of medications, were obtained from medical records. RESULTS: Demographic and epilepsy-related clinical variables had a strong influence (22-32%) on the cognition-related domain such as general adaptive function, school/total competence, and quality of life for cognitive function while a comparatively smaller effect (2-16%) on the more psychological domain including behavioral, emotional, and social variables. Younger age, shorter duration of illness, and smaller number of medications showed a strong positive impact on psychosocial function in pediatric epilepsy, particularly for adaptive function, competence, and quality-of-life aspects. CONCLUSION: Given the wide range of impact of demographic and clinical variables on various facets of psychosocial functions, more specific understanding of the various aspects of factors and their particular pattern of influence may enable more effective therapeutic approaches that address both the medical and psychological needs in pediatric epilepsy.

Respiratory syncytial virus-related encephalitis: magnetic resonance imaging findings with diffusion-weighted study.

INTRODUCTION: Respiratory syncytial virus (RSV) is a common pathogen causing acute respiratory infection in children. Herein, we describe the incidence and clinical and magnetic resonance imaging (MRI) findings of RSV-related encephalitis, a major neurological complication of RSV infection. METHODS: We retrospectively reviewed the medical records and imaging findings of the patients over the past 7 years who are admitted to our medical center and are tested positive for RSV-RNA by reverse transcriptase PCR. In total, 3,856 patients were diagnosed with RSV bronchiolitis, and 28 of them underwent brain MRI for the evaluation of neurologic symptoms; 8 of these 28 patients had positive imaging findings. Five of these 8 patients were excluded because of non-RSV-related pathologies, such as subdural hemorrhage, brain volume loss due to status epilepticus, periventricular leukomalacia, preexisting ventriculomegaly, and hypoxic brain injury. RESULTS: The incidence of RSV-related encephalitis was as follows: 3/3,856 (0.08 %) of the patients are positive for RSV RNA, 3/28 (10.7 %) of the patient underwent brain MRI for neurological symptom, and 3/8 (37.5 %) of patients revealed abnormal MR findings. The imaging findings were suggestive of patterns of rhombenmesencephalitis, encephalitis with acute disseminated encephalomyelitis, and limbic encephalitis. They demonstrated no diffusion abnormality on diffusion-weighted image and symptom improvement on the follow-up study. CONCLUSION: Encephalitis with RSV bronchiolitis occurs rarely. However, on brain MRI performed upon suspicion of neurologic involvement, RSV encephalitis is not infrequently observed among the abnormal MR findings and may mimic other viral and limbic encephalitis. Physicians should be aware of this entity to ensure proper diagnosis and neurologic care of RSV-positive patients.

Saethre­Chotzen syndrome with an atypical phenotype: identification of TWIST microdeletion by array CGH.

Saethre­Chotzen syndrome is a very rare autosomal dominant congenital disorder characterized by craniosynostosis and acrocephalosyndactyly. It is caused by a mutation in TWIST1, located on chromosome 7p21. A shortage of functional TWIST1 protein affects the development and maturation of cells in the skull, face, and limbs. The patient described in this report displayed craniofacial features classic for Saethre­Chotzen syndrome, including craniosynostosis, low-set ears, small pinna with prominent crura, a high-arched palate, and a simian crease on the left hand. He did not have the limb anomalies commonly seen in patients with Saethre­Chotzen syndrome, and the results of conventional chromosome analysis were normal. However, results of a microarray-based comparative genomic hybridization (array CGH) study confirmed the karyotype of46,XY.7p21.1p15.3(15,957,375-20,331,837)x1, a region that includes TWIST1. Subsequent fluorescent in situ hybridization analysis confirmed this result. No other chromosome was involved in the rearrangement. This case illustrates the important contribution of array CGH to the identification of TWIST microdeletions, even in a patient not showing the phenotype typical of Saethre­Chotzen syndrome.

Korean Developmental Screening Test for Infants and Children (K-DST): development, applications, and implications for future early childhood development interventions.

Evidence of the importance of early childhood development (ECD) has transformed child health monitoring and screening tools. Development of the Korean Developmental Screening Test for Infants and Children (K-DST) has expanded the applications of child health screening to a large number of infants and children in Korea and is contributing to the early detection of neurodevelopmental disorders and delivery of timely interventions. The previous screening tool (Korean Ages and Stages Questionnaire) raised some concerns, as its lack of consideration of the cultural background of the Korean population can lead to inaccurate or imprecise diagnoses. The K-DST, a tailored tool for Korean infants and children, is a simple and cost-efficient solution for child health monitoring and screening. This review focuses on the development and role of the K-DST in ensuring ECD. Here we review use of the K-DST for ECD screenings and discuss the best strategy for its use in other countries.

Prevalence and clinical characteristics of primary headaches among school children in South Korea: a nationwide survey.

OBJECTIVES: To determine the 1-year prevalence of headache and clinical characteristics of primary headaches among school children in South Korea. BACKGROUND: Many population-based studies have estimated the 1-year prevalence of headache, migraine, and tension-type headache (TTH). The results of those studies vary in terms of race and region. There have been few epidemiological population-based studies of headache in children and adolescents in Korea. METHODS: We conducted a cross-sectional school-based study of a randomized and proportional sample of 5360 boys and girls. All 180 sampled schools participated in this study. The questionnaires collected demographic data in addition to specific questions about headache according to the International Classification of Headache Disorder criteria, 2nd Edition. Valid questionnaires were returned by 94.1% of the sample population. Modified criteria changed the "duration" of migraine (>1 hour instead of 4 hours). RESULTS: The prevalence of headache among school children was 29.1% (1465/5039) in South Korea. The prevalence of headache in girls (33.4%) was significantly higher than in boys (24.4%) (P<.001). The mean age of students with headaches (14.02±3.03) was significantly higher than students without headaches (12.73±3.36) (P <.001). The prevalence of headache according to region was 30.7% among students in urban, 31.2% in suburban, and 21.6% in rural areas. The prevalence of headache according to age was 20.8% among students ∼6-12 years, 32.0% ∼13-15 years, and 38.2% ∼16-18 years. The prevalence according to headache types was 8.7% (boys 7.0%, girls 10.3%) in migraine, 13.7% (boys 10.7%, girls 16.3%) in TTH, and 6.7% in others. The mean frequency, severity of headache, and duration of symptoms were significantly higher in girls than in boys (P<.001). CONCLUSIONS: Recurrent primary headaches are quite prevalent among school-aged children and adolescents in South Korea, and the prevalence rates are similar to those reported elsewhere. TTH was more common than migraine. The prevalence of migraine headache increased with age. The prevalence rate of headache in students in urban and suburban areas was significantly higher than the rate of students in rural areas.

Enterovirus 71-related encephalomyelitis: usual and unusual magnetic resonance imaging findings.

INTRODUCTION: Most enterovirus (EV) 71 infections manifest as mild cases of hand-foot-mouth disease (HFMD)/herpangina with seasonal variations, having peak incidence during the summer. Meanwhile, EV 71 may involve the central nervous system (CNS), causing severe neurologic disease. In many cases, enteroviral encephalomyelitis involves the central midbrain, posterior portion of the medulla oblongata and pons, bilateral dentate nuclei of the cerebellum, and the ventral roots of the cervical spinal cord, and the lesions show hyperintensity on T2-weighted and fluid-attenuation inversion recovery (FLAIR) images. Our goal was to review usual and unusual magnetic resonance (MR) findings in CNS involvement of enteroviral infection. METHODS: Among consecutive patients who had HFMD and clinically suspected encephalitis or myelitis and who underwent brain or spinal MR imaging, five patients revealed abnormal MR findings. Diffusion-weighted and conventional MR and follow-up MR images were obtained. From cerebrospinal fluid, stool, or nasopharyngeal swabs, EV 71 was confirmed in all patients. RESULTS: MR imaging studies of two patients showed hyperintensity in the posterior portion of the brainstem on T2-weighted and FLAIR images, which is the well-known MR finding of EV 71 encephalitis. The remaining three cases revealed unusual manifestations: leptomeningeal enhancement, abnormal enhancement along the ventral roots at the conus medullaris level without brain involvement, and hyperintensity in the left hippocampus on T2/FLAIR images. CONCLUSION: EV 71 encephalomyelitis shows relatively characteristic MR findings; therefore, imaging can be helpful in radiologic diagnosis. However, physicians should also be aware of unusual radiologic manifestations of EV 71.

Attention deficit hyperactivity disorder in epileptic children.

It is well-known that the prevalence of attention deficit hyperactivity disorder (ADHD) is higher in epileptic children than in the general pediatric population. The aim of this study was to compare the accompaniment of ADHD in epileptic children with well-controlled seizures and no significant intellectual disability with that in healthy controls. We included epileptic children between the ages of 6 and 12 yr visiting our clinic for six consecutive months and controls without significant medical or psychiatric illnesses. We excluded patients with intellectual disability or persistent seizures during the recent three months. The diagnosis of ADHD was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). After exclusion of 84 patients, we enrolled 102 (54.8%) children (mean age, 9.4 ± 2.0 yr). Seven (7 of 102, 6.9%) were diagnosed with ADHD. As compared to control group (4 of 110, 3.6%), there was no difference in ADHD accompaniment (P = 0.29). No difference was observed in ADHD accompaniment according to seizure type and epilepsy syndrome. In conclusion, the accompaniment of ADHD in epileptic children with well-controlled seizures and no intellectual disability may not differ from that of the general pediatric population.

Novel Pathogenic Variant (c.1171A>T) in PHF21A in a Female with Intellectual Disability and Craniofacial Anomalies.

Background: PHF21A, along with EXT2 and ALX4, is one of the causative genes of Potocki-Shaffer syndrome (PSS), a rare contiguous disorder involving chromosome region11p11.2. PHF21A has been associated with intellectual developmental disorders and craniofacial anomalies and suggested as a candidate for more extended phenotypes. However, variants in PHF21A and its associated phenotypes are yet to be fully explored, since reports on cases with variants affecting this gene are few worldwide. We present a novel heterogeneous variant in PHF21A in a 26-year-old Korean female. Methods: The patient's clinical manifestations were recorded and physical examination, cognitive assessment, brain imaging, metabolic screening, and cytogenetic testing including whole exome sequencing were pursued. Results: Whole exome sequencing identified a de novo nonsense variant c.1171A>T (p.Lys391Ter), affecting the AT-hook domain. The patient showed an extended phenotypic spectrum along with intellectual developmental disorders and craniofacial anomalies, such as attention-deficit hyperactivity disorder, epilepsy, overgrowth, and hypotonia. Variants affecting the AT-hook domain are few in PSS, however, the phenotypic spectrum of the patient was in line with previously reported cases. Conclusion: This case further reinforced and adds to the extended data on the phenotypes associated with PHF21A haploinsufficiency.

Evaluation of users' level of satisfaction for an artificial intelligence-based diagnostic program in pediatric rare genetic diseases.

The artificial intelligence (AI)-based genetic diagnostic program has been applied to genome sequencing to facilitate the diagnostic process. The objective of the current study was to evaluate the experience and level of satisfaction of participants using an AI-based diagnostic program for rare pediatric genetic diseases. The patients with neurodevelopmental disorders or hearing impairments, their guardians, and their physicians from 16 tertiary general hospitals were enrolled. The study period was from April 2020 to March 2021. A survey was designed to assess their experience and level of satisfaction. A total of 30 physicians and 243 patients and guardians (199 neurodevelopmental disorders and 44 hearing impairments) completed the survey. DNA samples of the subjects were collected through buccal swabs or blood collection: 211 subjects (86.8%) through buccal swab and 29 subjects (11.9%) through blood collection. Average turnaround time for result receipt was 57.54 ± 32.42 days. For the sampling method, 193 patients and guardians (81.1%) and 28 physicians (93.3%) preferred buccal swab. The level of satisfaction of the 2 groups participating in the AI-based diagnostic program was 8.31 ± 1.71 out of 10 in the patient and guardian group and 8.42 ± 1.23 in the physician group. Clinicians, patients, and guardians are satisfied with the AI-based diagnostic program in general. With an increase in AI-based precision medicine solutions, the evaluation of the user's satisfaction with appropriate provision will help improve personal health care.

The role of neuroimaging in children and adolescents with recurrent headaches--multicenter study.

OBJECTIVES: To evaluate the role of neuroimaging and to estimate the prevalence of significant and treatable intracranial lesions in children and adolescents with recurrent headaches. BACKGROUND: Neuroimaging studies are commonly performed in children and adolescent patients with headache because of increasing demands by parents and physicians, although objective data and studies to support this widespread practice are minimal. METHODS: We retrospectively reviewed the medical records of all 1562 (male 724, female 838) new patients presenting with recurrent headaches to 9 Pediatric Neurology Clinics of tertiary Hospitals. Data regarding age of onset, duration of symptoms before presentation, frequency, duration of each episode, intensity, location and quality of headache, associated neurologic symptoms and a comprehensive neurological examination were obtained for each patient. The International Classification of Headache Disorders, second edition, was used to classify headache types. RESULTS: Neuroimaging procedures were performed in 77.1% of the patients. Overall, 9.3% (112/1204) of the patients had abnormal findings from neuroimaging. The highest yield was in patients with an abnormal neurological examination wherein abnormal findings on neuroimaging were seen in 50.0% (9/18) of patients (P < .001). The yield was low when imaging was carried out in view of changes in the type of headache (12.9% [26/201]), neurologic dysfunction (10.8% [9/83]), recent onset of severe headaches (7.0% [12/171]), and demands of parent and physicians (10.1% [21/208]). Eleven patients underwent surgery based on neuroimaging results. There was no significant relation between abnormality on neuroimaging and age, sex, headache type, age of onset of headache, duration of symptoms before presentation, duration, frequency, location and intensity of headache (P > .05). CONCLUSIONS: Neuroimaging procedures in children and adolescents with headaches, although not always required, are very commonly performed. We suggest that more strict guidelines for rational use of neuroimaging are needed for pediatric headache patients.

Development of the Parental Questionnaire for Cerebral Visual Impairment in Children Younger than 72 Months.

BACKGROUND AND PURPOSE: Cerebral visual impairment (CVI) is an underdiagnosed condition in children, and its assessment tools have focused on older children. We aimed to develop a parental questionnaire for cerebral visual impairment (PQCVI) for screening CVI in young children. METHODS: The PQCVI comprised 23 questions based on a modified version of Houliston and Dutton's questionnaire for older children. The PQCVI with neurocognitive function tests was applied to 201 child-parent pairs with typically developing children younger than 72 months (age 32.4±20.1 months, mean±standard deviation). The children were classified into six age groups. The normative data, cutoff scores, and internal reliability were assessed and item analysis was performed. We referred to the total score for all questions as the cerebral visual function (CVF) score. RESULTS: The normative data showed that the CVF score and the scores corresponding to ventral-stream and dorsal-stream visual functions plausibly increased with age. The scores rapidly reached 90% of their maximum values up to the age of 36 months, after which they increased slowly. Cronbach's alpha for all questions across all age groups was 0.97, showing excellent consistency. The item difficulty and item discrimination coefficients showed that the questions were generally adequate for this age stage. CONCLUSIONS: The PQCVI items produced reliable responses in children younger than 72 months. The rapid increase in scores before the age of 3 years supports the importance of early identification of CVI. Following additional clinical verification, the PQCVI may be useful for CVI screening.

Percutaneous Endoscopic Gastrostomy and Nutritional Interventions by the Pediatric Nutritional Support Team Improve the Nutritional Status of Neurologically Impaired Children.

AIM: To evaluate the long-term effects of nutritional improvement following percutaneous endoscopic gastrostomy (PEG) tube feeding stratified by previous feeding method and to assess the impact of underlying muscle tone on the outcomes of the nutritional intervention. METHODS: Neurologically impaired children who underwent PEG tube insertion and nutritional intervention provided by a pediatric nutritional support team were enrolled. We measured anthropometric variables, laboratory parameters, and nutritional intake at baseline, 6 months after PEG insertion, and the last visit. We evaluated the percent ideal body weight (PIBW), body mass index (BMI)-for-age z-score, and percentiles and calculated the ratios of calorie intake compared to required requirement (CIR) and protein intake compared to recommended requirement (PIR). RESULTS: The PIBW and BMI-for-age z-score improved during the first 6 months (p = 0.003 and p = 0.005, respectively). The CIR (p = 0.015) and PIR (p = 0.004) increased during the study period. The baseline BMI and PIBW of the previous nasogastric tube feeding group were better than those of the oral feeding group (p = 0.02 and p = 0.03, respectively). The BMI-for-age z-score, PIBW, CIR, and PIR improved in the hypertonic group (p = 0.03, 0.02, 0.03, and 0.01, respectively). CONCLUSION: PEG tube feeding and active nutritional intervention improved the nutritional status of neurologically impaired children immediately after PEG insertion. The nutritional requirements might vary by the muscle tonicity.