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Headache is a common complaint in childhood and adolescence. Differentiating benign primary headaches from ominous secondary headaches is often difficult. Clinicians usually seek red flags to determine the need for neuroimaging. We aimed to evaluate the diagnostic values of red flags in pediatric headaches.We retrospectively reviewed the medical records of 1510 pediatric patients (1470 with primary headache, 40 with secondary headache) presenting with headache and underwent neuroimaging from two centers between March 2010 and December 2019.The secondary-headache group exhibited significantly higher frequencies of abnormal neurologic signs/symptoms (40.0% vs 6.8%, p 0.001), Valsalva maneuver/exercise-induced headache (15.0% vs 4.9%, p = 0.004), headache with vomiting (35.0% vs 17.9%, p = 0.006), and onset under age 6 (25.0% vs 10.3%, p = 0.003) than the primary-headache group, with the following positive likelihood ratio (PLR): 5.88, 3.06, 1.96, and 2.42, respectively. The sensitivity values were as follows: abnormal neurologic signs/symptoms (16/40, 40.0%), headache with vomiting (14/40, 35.0%), onset under age 6 (10/40, 25.0%), and Valsalva maneuver/exercise-induced headache (6/40, 15.0%). The overall sensitivity for ominous secondary headaches requiring surgical treatment was 86.2% (25/29).Certain red flags, including abnormal neurologic signs/symptoms, Valsalva maneuver/exercise-induced headache, headache with vomiting, and onset under age 6, were more prevalent in the secondary-headache group; nonetheless, their sensitivity values and PLR were relatively low. Notwithstanding, considering these red flags' high overall sensitivity for ominous secondary headaches, neuroimaging in patients presenting these red flags should rely on careful follow-up of symptom progression.

Background Tic disorders are childhood-onset neuropsychiatric disorders characterized by multiple motor or vocal tics with frequent comorbidities and a broad spectrum of phenotypic presentations. In this study, we aimed to investigate the clinical characteristics and comorbid neuropsychiatric conditions in pediatric patients with tic disorders. Methods We retrospectively reviewed the medical records of 119 pediatric patients (89 males, 30 females) who were diagnosed with tic disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) at Uijeongbu St. Mary’s Hospital, Republic of Korea, between January 2012 and July 2019. Results The mean age of tic onset was 6.9 years (range, 1–14) and the mean age at diagnosis was 8 years (range, 1–17). The mean lag between tic onset and diagnosis was 13.3 months (range, 0.25–132). The most common, first-presenting tics were eye blinking (50.4%), followed by jaw or lip movement (29.4%) and throat clearing (29.4%). Thirty-seven (31.1%) patients had at least one co-occurring neuropsychiatric disorder at the time of tic diagnosis. Subtypes of tic disorders, types of initial tics, and presence of neuropsychiatric comorbidities were not associated with tic severity. Tic severity was associated with greater functional impairment and tic noticeability (p p = 0.11). Conclusions The evolving nature of tic expression and severity, high prevalence of neuropsychiatric comorbidities, and associated functional impairments emphasize the importance of comprehensive assessment during the disease course for determining and prioritizing goals of treatment.

Background: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by a triad of social, communicative, and imaginative impairments. Although early detection and intervention are important to improve functional outcomes in ASD, similar features between ASD and other developmental delays may impede timely diagnosis. In this study, we aimed to investigate the feasibility of Cognitive Visual Assessment Questionnaire (CVAQ) in differentiating ASD from other developmental delays.Methods: We retrospectively reviewed the medical records of 115 pediatric patients (80 males, 35 females) with ASD and other developmental delays who had the Modified Checklist for Autism in Toddlers (M-CHAT) and CVAQ performed at Uijeongbu St. Mary's Hospital from January 2017 to June 2019. Results: The mean age at M-CHAT and CVAQ was 31.8 months (range, 14.1 – 48). The proportion of ASD was significantly higher in patients with screen-positive M-CHAT than those with screen-negative M-CHAT (P = 0.035). The sensitivity of CVAQ for detecting ASD was 83.3% and 94.1% in 14.1 – P = 0.437).Conclusions: Our study demonstrates that autistic individuals may have a specific impairment in dorsal stream functioning. CVAQ also showed improved sensitivity for detecting ASD in toddlers. When coupled with clinical observation and judgement, CVAQ is a useful alternative screening tool for differentiating ASD from other developmental delays in young children.

Background Tic disorders are childhood-onset neuropsychiatric disorders characterized by multiple motor or vocal tics with frequent comorbidities and a broad spectrum of phenotypic presentations. In this study, we aimed to investigate the clinical characteristics and comorbid neuropsychiatric conditions in pediatric patients with tic disorders. Methods We retrospectively reviewed the medical records of 119 pediatric patients (89 males, 30 females) who were diagnosed with tic disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-Ⅴ) at Uijeongbu St. Mary’s Hospital, Republic of Korea, between January 2012 and July 2019. Statistical comparisons were performed using Fisher’s exact test, Pearson’s chi-square test, Student’s t-test, and the Kruskal-Wallis test. Spearman’s rank correlation coefficient was used to conduct correlational analyses. Results The mean age of tic onset was 6.9 years (range, 1–14) and the mean age at diagnosis was 8 years (range, 1–17). The mean lag between tic onset and diagnosis was 13.3 months (range, 0.25–132). The most common, first-presenting tics were eye blinking (50.4%), followed by jaw or lip movement (29.4%) and throat clearing (29.4%). Thirty-seven (31.1%) patients had at least one co-occurring neuropsychiatric disorder at the time of tic diagnosis. Subtypes of tic disorders, types of first-presenting tics, and presence of neuropsychiatric comorbidities were not associated with tic severity. Tic severity was associated with greater functional impairment and tic noticeability (P P = 0.110). Conclusions The evolving nature of tic expression and severity, high prevalence of neuropsychiatric comorbidities, and associated functional impairments emphasize the importance of comprehensive assessment during the disease course for determining and prioritizing goals of treatment.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare autoimmune disorder manifesting as seizures, movement disorders, and psychiatric changes. However, there have been few case reports concerning this disorder in South Korean children. The current case report describes a pediatric patient with anti-NMDAR encephalitis. A 13-year-old female patient developed clonic movements of the right arm followed by aphasia, paresthesia, and right-sided hemiparesis. The electroencephalogram (EEG) results indicated electroclinical seizures arising from the left temporal area. Brain magnetic resonance imaging (MRI) revealed high signal intensity and cortical swelling in left temporal lobe. Anti-NMDAR antibodies were detected in the cerebrospinal fluid (CSF). The patient was treated with intravenous immunoglobulin and high-dose methylprednisolone and showed partial improvement in language skills, paresthesia, and motor power. The brain MRI and EEG results also indicated improvement. However, anti-NMDAR antibodies persisted in the CSF. After four doses of rituximab, the patient exhibited complete recovery of language and motor skills, and was seizure free under treatment with antiepileptic medication. There were no residual anti-NMDAR antibodies in the CSF at her 24-month follow-up visit. This case report elucidates the benefits of early intervention using rituximab to improve neurological deficits and achieve baseline recovery in patients with anti-NMDAR encephalitis.

Background and Purpose The modified Atkins diet is a less restrictive alternative to the ketogenic diet (KD), allowing unlimited protein, fat, calories, and fluid intake. Moreover, it can be started on an outpatient basis without requiring a fast. This study evaluated the efficacy, tolerability, and compliance of the modified Atkins diet in intractable pediatric epilepsy. Methods We retrospectively reviewed the medical records of 26 pediatric patients (10 males and 16 females) with intractable epilepsy who were treated using the modified Atkins diet at Samsung Medical Center from January 2011 to March 2017. Results The mean age at initiation of the modified Atkins diet was 10.9 (range, 2–21) years. The diet was continued for a mean duration of 5.9 (range, 1–16) months. After 6 months, 10 (38.5%) remained on the diet, of whom six (60%) had > 50% seizure reduction and two (20%) became seizure free. Four of 26 patients (15.4%) reported side effects of the diet, including constipation (n = 2) and lipid profile elevations (n = 2). Mean body mass index (BMI) was reduced from 22.6 to 20.9 kg/m2 (p < 0.05) in 13 patients who continued the diet for ≥ 3 months. Four of these patients (30.8%) were overweight (BMI > 25 kg/m2) before initiating the diet and were satisfied with their BMI changes from a mean of 30.3 to 27 kg/m2 (p < 0.05). Food refusal (n = 3) and poor parental compliance (n = 3) were the common reasons cited for cessation. Conclusions The modified Atkins diet may be an alternative treatment option for children with intractable epilepsy who are unable to tolerate KD because of food intake-related restrictiveness or adverse effects. The continuous support of healthcare professionals and families plays a key role in diet maintenance.

Turner syndrome (TS) is a genetic disorder with phenotypic heterogeneity caused by the monosomy or structural abnormalities of the X chromosome, and it has a prevalence of about 1/2500 females live birth. The variable clinical features of TS include short stature, gonadal failure, and skeletal dysplasia. The association with growth hormone (GH) deficiency or other hypopituitarism in TS is extremely rare, with only a few case reports published in the literature. Here, we report the first case of a patient with mosaic TS with complete GH deficiency and pituitary microadenoma, and we include the literature review. During the work-up of the patient for severe short stature, three GH provocation tests revealed peak GH levels of less than 5 ng/mL, which was compatible with complete GH deficiency. Sella magnetic resonance imaging showed an 8 mm non-enhancing pituitary adenoma with mild superior displacement of the optic chiasm. Karyotyping revealed the presence of ring chromosome X and monosomy X (46,X,r(X)/45,X/46,X,psu dic r(X;X)), which indicated a mosaic TS. It is important to consider not only chromosome analyses in females with short stature, but also the possibility of the coexistence of complete GH deficiency accompanying pituitary lesions in TS. In conclusion, the present study reports the first case of GH deficiency and pituitary adenoma in a patient with rare mosaic TS, which extends the genotype–phenotype spectrum for TS.

Super-refractory status epilepticus (SRSE) is one of the most challenging issues in intensive care units (ICUs) in that it is associated with high morbidity and mortality. Although the ketogenic diet (KD) has been reported to be effective in treating of SRSE, the use of the diet as therapy can be complicated by concomitant medical problems specific to critically ill patients. In this study, we aimed to describe our experience of the KD for SRSE patients in ICUs.We retrospectively reviewed the medical records of 16 patients (10 males, 6 females) with SRSE who were treated with the KD in the ICUs at Samsung Medical Center from July 2005 to July 2017.The median age of seizure onset was 8 years (interquartile range 5-13.5). Prior to diet initiation, the patients were in convulsive or non-convulsive SRSE for a median of 23 days (range, 3-420). The median time to achieve ketosis was 3 days (range, 2-6). The KD was continued for a median of 2.1 months (range, 0.1-15.8). Of the 16 patients, nine (56.3%) achieved seizure freedom, six (37.5%) reported50% seizure reduction, and one (6.2%) had50% seizure improvement after the KD. There was no significant change in the number of antiepileptic drugs. The most commonly encountered complication during the KD was gastrointestinal disturbance.Our experience indicates that the KD is an effective alternative therapeutic strategy for SRSE patients in ICUs with adequate efficacy and safety in reducing seizure frequency and weaning from prolonged mechanical ventilation, although functional outcome was not favorable for most patients. Close monitoring and preventive management of potential adverse effects are critical elements for success with the KD in patients with SRSE.

The role of unrelated donor HSCT for children with de novo AML in CR1 is controversial. We performed this study to investigate the feasibility of unrelated donor HSCT who initially had intermediate- or high-risk cytogenetics. We retrospectively reviewed medical records of patients with AML who received unrelated HSCT in CR1 at Samsung Medical Center between November 2001 and January 2012. Patients were allocated based on karyotype at diagnosis as follows: (a) low-risk: inv(16), t(16;16), t(8;21), and t(15;17); (b) high-risk: -5, 5q-, -7, 3q abnormalities, t(8;16), t(6;9), t(6;11), t(6;21), t(10;11), complex karyotype (≥3 abnormalities), and acute megakaryocytic leukemia without t(1;22); and (c) IR: all the other karyotypes including normal. Patients in intermediate- or high-risk group who were transplanted with either unrelated CB or matched unrelated BM/mobilized PB in their CR1 were included in this study. The projected OS and EFS rates were 74.9% and 71.1%, respectively, with a median follow-up of 87.3 months after transplantation. The EFS was 70.1%, 80.7%, and 73.9% for CB, BM, and mobilized PB groups, respectively (P = 0.89), and 73.9% and 70.6% for IR and high-risk groups (P = 0.76). The leading cause of death was relapse (n = 8), and only one patient died from non-relapse cause. Unrelated donor HSCT seems a feasible approach for children with intermediate- or high-risk AML in CR1. Relapse remains the leading cause of treatment failure among these patients.

Preparation of functionalized graphene by electrochemical exfoliation of graphite rod using sodium dodecyl benzene sulfonate (SDBS) is reported. SDBS solution has been used as the electrolyte as well as functional groups. SDBD is an anionic surfactant which helps to provide uniform dispersion in water and prevents the π-π π-π stacking as well. XRD result indicates the formation of graphene whereas; the functionalization of graphene was confirmed through the FT-IR spectrum, which shows presence of peaks corresponding to SO3-. UV-vis spectroscopy demonstrates the dispersibility of SDBS-functionalized graphene, and peaks of SDBS and graphene appeared at 225 nm and 260nm, respectively. Raman spectroscopy show ID/IGIDIG ratio is < 1. It means that defects of SDBS-functionalized graphene are reduced.

Human umbilical cord is easy to obtain because it is discarded after birth, so it can avoid the ethical issues. Chondrogenesis studies using MSCs from bone marrow, cord blood, adipose has been indicated that TGFβ3 and BMP6 stimulate chondrogenesis. Therefore, we investigated chondrogenesis of the hUC-MSCs on TGFβ3, BMP6 and combination of the two growth factors. We initiated chondrogenesis of the cells by giving physical forces to form 3D cell clusters. After the initiation, we gave four experimental groups for differentiation of the cells as follows; control, 10 ng/mL TGFβ3, 100 ng/mL BMP6, and the combination of 5 ng/mL TGFβ3 and 50 ng/mL BMP6. To analyze of the chondrogenesis, GAG contents, mRNA expression, histological and immunohistochemistry (IHC) were performed. To analyze GAG contents, GAG assay was measured and RT-PCR was performed to determine the chondrogenic markers. Histological analysis was performed through safranin O, alcian blue, and IHC was performed using collagen type I and II. GAG contents were increased that 184% by TGFβ3, 147% by BMP6 and 189% by the combination of TGFβ3 and BMP6 compared to control. The growth factors improved collagen II and aggrecan expression, especially, TGFβ3 and BMP6 were shown synergistic effect compared to only TGFβ3 or BMP6 treated. The histological and IHC analysis indicated that the chondrogenic differentiation in the TGFβ3 and the combination of TGFβ3 and BMP6 showed more cartilage deposition. In conclusion, TGFβ3 and BMP6 differentiated hUC-MSCs into chondrogenic clusters of the combination treatment of the two growth factors showed more efficient chondrogenic ability.

Hypophosphatasia is a rare hereditary disorder characterized by defective bone and tooth mineralization and deficiency of tissue non-specific alkaline phosphatase activity. The prognosis for the infantile form is poor, with approximately 50% of patients dying within the first year of life from respiratory failure. We describe the clinical and biochemical findings as well as the molecular analysis of a Korean boy with infantile hypophosphatasia and present a literature review. A 1-month-old boy visited the clinic because of poor feeding, frequent vomiting, hypotonia, and failure to thrive from birth. Laboratory tests revealed high total calcium, low phosphorous, low alkaline phosphatase, low parathyroid hormone, and normal 25-hydroxyvitamin D. Intravenous hydration with normal saline was started, and dietary calcium intake was restricted. Skeletal X-rays showed a markedly increased distance of the anterior fontanelle, impaired mineralization, and rachitic changes in the metaphyses. By Sanger sequencing of the ALPL gene, we identified two heterozygous variants, including a missense (c.334GA; p.Gly112Ser) and a nonsense (c.1039CT; p.Gln347*) variant. The c.334GA (p.Gly112Ser) variant had previously been reported in a patient with lethal type hypophosphatasia, while the nonsense c.1039CT (p.Gln347*) variant was novel. In the current case, the accurate diagnosis and prompt intervention-including dietary calcium intake restriction, tracheostomy to prevent progression to respiratory failure, and fundoplication with gastrostomy to ensure the administration of adequate calories-seemed to play an important role for avoiding preventable morbidity and premature mortality.

Paroxysmal nonepileptic events (PNEs) are frequently encountered phenomena in children. Although frequencies and types of PNEs have been extensively studied in adult populations, the data available for children and adolescents are limited, especially in patients without underlying neurologic disorders. In this study, we evaluated and compared the characteristics of PNEs between age groups and according to the presence of neurologic deficits to improve early detection and diagnosis of PNEs.We retrospectively reviewed 887 pediatric patients who were admitted to the epilepsy monitoring unit at the Samsung Medical Center between December 2001 and July 2014. One hundred and forty-one patients (15.9%) were diagnosed as having PNEs on the basis of their clinical history and long-term video-electroencephalography (EEG) monitoring (VEM).Children with PNEs were divided into three groups by age: 1) the infant, toddler, and preschool group (6 years, N=50, 35.5%); 2) the school-age group (6-12 years, N=30, 21.3%); and 3) the adolescent group (12-18 years, N=61, 43.3%). Physiologic disorders, such as normal infant behavior, sleep movement, and staring, were more common in patients younger than 6 years of age, whereas psychogenic nonepileptic seizures were predominant in patients older than 6 years. Vasogenic syncope was also frequently observed in the adolescent group and was confirmed by the head-up tilt test. There was no significant difference in specific PNE types between the groups of patients with or without neurologic deficits.Physiologic symptoms were predominant in the younger age group, whereas psychogenic nonepileptic seizures were observed in older age groups more often. Clinical pattern recognition by age plays an important role in clinical practice, because pediatric patients present various types of PNEs with age-specific patterns. Considering various and inconsistent presentations and the importance of correct diagnosis, long-term VEM can be helpful in diagnosing normal infant behavior and psychogenic nonepileptic seizures.

Background and purpose Antiepileptic drug (AED)-associated cutaneous adverse drug reactions can lead to the discontinuation of medications. The aim of this study was to determine the long-term efficacy and safety of performing desensitization to oxcarbazepine. Methods This study involved 20 patients who exhibited cutaneous adverse drug reactions associated with oxcarbazepine use between July 2009 and March 2016 at Samsung Medical Center. All of the participants had to discontinue oxcarbazepine despite presenting initially positive responses. Human leukocyte antigen genotyping was performed to detect the genetic predisposition to Stevens-Johnson syndrome. The desensitization to oxcarbazepine was performed with a starting dosage of 0.1 mg/day. Efficacy was evaluated by comparing the frequency of seizures before and at 1 and 3 years after desensitization. Adverse events occurring during desensitization and the retention rate after desensitization were also investigated. Results Nineteen patients (95%) safely completed the desensitization protocol. One withdrew owing to emotional problems that appeared to be associated with oxcarbazepine. The follow-up period was 4.6±1.2 years (mean±SD), and oxcarbazepine was maintained for more than 3 years after desensitization in 15 patients (83.3%). The response rates were 84.2% and 77.8% at 1 and 3 years after desensitization, respectively. Eight patients remained seizure-free for 3 years, and two discontinued all AEDs. Transient adverse reactions such as mild rash and itching were reported by five patients during desensitization. Conclusions This study has demonstrated the long-term efficacy and safety of desensitization to oxcarbazepine in patients exhibiting cutaneous adverse drug reactions. This favorable outcome should encourage the implementation of desensitization in patients presenting with hypersensitivity to oxcarbazepine as an alternative strategy in clinical practice.

A Gram-negative bacterium was isolated from the blood of a patient with diabetes mellitus. However, it could not be identified by conventional microbiological methods, and so was characterized by phenotypic and genotypic analyses. 16S rRNA gene sequence analysis revealed that the strain belonged to the genus Neisseria. Based on the phenotypic and genotypic characteristics, we propose that strain SMC-A9199T (=KCTC 22696T=JCM 16127T) should be classified as a novel species, ‘Neisseria skkuensis’ sp. nov. The patient was further treated with amoxicillin–clavulanate and ciprofloxacin for 3 weeks.