Inhibitory Effect of Insulin Treatment on Apoptosis of Intervertebral Disc Cells in a Streptozotocin-Induced Diabetic Rat Model

Methods@#Rats were allocated randomly into one of three groups: control, STZ, and STZ-insulin. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in the STZ and STZ-insulin groups. The blood glucose level was consistently above 400 mg/ dL in the STZ and STZ-insulin groups 2 weeks after STZ injection. After 2 weeks of STZ injection, the STZ-insulin group was administered insulin treatment (1.5 unit/100 g) daily for up to 4 weeks. Blood glucose of the STZ-insulin rats significantly decreased to normal levels 4 weeks after insulin treatment. The rats were sacrificed 6 weeks after STZ injection, and disc cells and tissues were harvested to investigate the expression of apoptosis markers and matrix metalloproteinases (MMPs). @*Results@#Fas and caspase-8, -9, and -3 expressions were significantly increased in the STZ group, along with increased expressions of MMP-2 and -3. On the contrary, insulin treatment significantly decreased the expressions of Fas, caspase-8, -9, and -3 as well as MMP-2 and -3 in the STZ-insulin group. @*Conclusions@#The results of the current study demonstrated that insulin treatment attenuates excessive apoptosis of disc cells and matrix degradation in the diabetic rat model. Accordingly, strict blood glucose control should be recommended to prevent disc degeneration in diabetic patients.

Is the Diagnostic Trial with Proton Pump Inhibitors Reasonable for School Age Children with Gastroesophageal Reflux Symptoms? / 대한소아소화기영양학회지

PURPOSE: On the basis of evidence, we aimed to reevaluate the necessity of the empirical proton pump inhibitor (PPI) trial for children with suspected gastroesophageal reflux disease (GERD). METHODS: We analyzed the frequency of GERD in 85 school-age children with gastroesophageal reflux (GER) symptoms, who received 24-hour esophageal pH monitoring and/or upper endoscopy. According to the reflux index (RI), the children were classified into normal (RI <5%), intermediate (5%≤ RI <10%), or abnormal (RI ≥10%) groups. RESULTS: Fifty six were female and 29 were male. Their mean age was 12.6±0.5 (±standard deviation) years (range: 6.8–18.6). The RI analysis showed that the normal group included 76 patients (89.4%), the intermediate group included 6 patients (7.1%), and the abnormal group included 3 patients (3.5%). The DeMeester score was 5.93±4.65, 14.68±7.86 and 40.37±12.96 for the normal, intermediate and abnormal group, respectively (p=0.001). The longest reflux time was 5.56±6.00 minutes, 9.53±7.84 minutes, and 19.46±8.35 minutes in the normal, intermediate, and abnormal group, respectively (p=0.031). Endoscopic findings showed reflux esophagitis in 7 patients. On the basis of the Los Angeles Classification of Esophagitis, 5 of these patients were included in group A, 1 patient, in group B and 1 patient, in group C. CONCLUSION: The incidence of GERD was very low in school-age children with GER symptoms. Therefore, injudicious diagnostic PPI trials would be postponed until the actual prevalence of GERD is verified in future prospective studies.

The Prognostic Factors Affecting the Occurrence of Subsequent Unprovoked Seizure in Patients Who Present with Febrile Seizure after 6 Years of Age / 대한소아신경학회지

PURPOSE: Few reports have described the prognostic factors affecting the occurrence of subsequent unprovoked seizure in patients who present with febrile seizure (FS) after 6 years of age. We investigated the prognostic factors affecting the development of unprovoked seizures after FS among patients from Jeju Island. METHODS: We included patients who developed FS after 6 years of age, who presented to our outpatient clinic between January, 2011 and June, 2017. Clinical data were obtained through chart reviews and phone call interviews. We used logistic regression analysis to analyze the risk factors associated with the occurrence of subsequent unprovoked seizure. RESULTS: Of the 895 patients who presented to our hospital due to their febrile seizure, 83 developed FS after 6 years of age. Among them, 3 patients were prescribed antiepileptic drugs before the onset of the unprovoked seizure, and 4 patients developed an unprovoked seizure before 6 years of age. Thus, overall, 76 patients were included in the study. 51 patients developed first FS before 6 years of age. In the remaining patients, the first FS developed after 6 years of age. The mean observational period since the last outpatient follow-up visit was 3.2 years (median 3.04 years, range: 1.42-4.71 years). Among them, 21% developed an unprovoked seizure. Logistic regression analysis showed that electroencephalographic (EEG) abnormalities served as an independent risk factor for a subsequent unprovoked seizure. CONCLUSION: EEG is the proper diagnostic tool to predict the risk of a subsequent unprovoked seizure in patients with FS after 6 years of age.

Dizziness and orthostatic intolerance in pediatric migraine

Pediatric migraine is followed by more frequent episodes of dizziness or vertigo than tension-type headaches. Just as children with migraine show a high sensitivity to light and noise, they are also susceptible to vestibular stimuli, resulting in vertigo or dizziness. Previous studies have found vertigo to be more common among patients with migraine. Vestibular migraine and benign paroxysmal vertigo of childhood have been identified as the most common causes of vertigo in children without ear disease. Benign paroxysmal vertigo of childhood is also thought to be a precursor of later episodes of migraine. The term vestibular migraine was included as a part of the appendix in the International Classification of Headache Disorders 3rd edition beta version, as an increasing number of studies have shown a positive relationship between migraine and vertigo. However, vertigo cannot be easily identified by parents or pediatricians, as young children are unable to explain their vertigo- or migraine-related symptoms. This is also applicable to specialists such as pediatric neurologists and otolaryngologists, as they often do not know the exact definition of vertigo in such patients and cannot make the correct differential diagnosis. Consequently, the inadequate evaluation and treatment of these patients can lead to a high socioeconomic cost. This review article discussing vertigo in pediatric migraine will help more medical doctors to effectively examine, accurately diagnose, and promptly treat young children suffering from migraine or vertigo.

Sonographic Growth Charts for Kidney Length in Normal Korean Children: a Prospective Observational Study

Kidney length is the most useful parameter for clinical measurement of kidney size, and is useful to distinguish acute kidney injury from chronic kidney disease. In this prospective observational study of 437 normal children aged between 0 and < 13 years, kidney length was measured using sonography. There were good correlations between kidney length and somatic values, including age, weight, height, and body surface area. The rapid growth of height during the first 2 years of life was intimately associated with a similar increase in kidney length, suggesting that height should be considered an important factor correlating with kidney length. Based on our findings, the following regression equation for the reference values of bilateral kidney length for Korean children was obtained: kidney length of the right kidney (cm) = 0.051 × height (cm) + 2.102; kidney length of the left kidney (cm) = 0.051 × height (cm) + 2.280. This equation may aid in the diagnosis of various kidney disorders.

Kawasaki Disease with Acute Respiratory Distress Syndrome after Intravenous Immunoglobulin Infusion / 대한중환자의학회지

Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. We report a case of KD with acute respiratory distress syndrome (ARDS) after intravenous immunoglobulin (IVIG) infusion. Lung manifestations associated with KD have previously been reported in the literature. Although IVIG infusion is an effective therapy for acute KD, there are some reported complications related to IVIG infusion: hypotension, aseptic meningitis, acute renal failure, hemolytic anemia, etc. The case of KD reported here was treated with IVIG and aspirin. A few days after recovery from KD, the patient developed fever and maculopapular rash. A diagnosis of relapse KD was made and retreated with IVIG infusion. However, the patient developed ARDS four days after the second IVIG infusion. The patient recovered from ARDS after nine days of ICU care, which included high frequency oscillation ventilation with inhaled nitric oxide, steroid treatment and other supportive care.

Predictors of Recurrent Febrile Seizure / 대한소아신경학회지

PURPOSE: We performed this study to investigate the clinical features of febrile seizure (FS) and to identify prognostic factors of recurrence of FS on Jeju Island, South Korea. METHODS: A hospital-based retrospective study was performed in 307 children with FS whose first episode developed between July 2005 and June 2013 seen at the Pediatric Department of Jeju National University Hospital. RESULTS: 307 children (189 boys and 118 girls) were enrolled in this study. Based on first FS semiology, 97.1% (298/307) of cases manifested as generalized seizure and 2.9% of cases showed focal seizure. Moreover, 23.5% (72/307) of cases had complex FS as the first FS. The average age at the first FS was 18.4 months. A family history of FS or epilepsy was found in 30.6% and 5.2% of patients, respectively. Recurrence occurred in 67.6% of patients; among them, 93.7% had their first recurrence within 1 year. Multivariate analysis identified the following factors as significant predictors of recurrence of FS: early onset of FS (< or =15 months of age) and a family history of FS. CONCLUSIONS: We identified the following risk factors for recurrence of FS: early onset of FS (< or =15 months of age) and a family history of FS.

Systemic Classification for a New Diagnostic Approach to Acute Abdominal Pain in Children / 대한소아소화기영양학회지

PURPOSE: With previous methods based on only age and location, there are many difficulties in identifying the etiology of acute abdominal pain in children. We sought to develop a new systematic classification of acute abdominal pain and to give some helps to physicians encountering difficulties in diagnoses. METHODS: From March 2005 to May 2010, clinical data were collected retrospectively from 442 children hospitalized due to acute abdominal pain with no apparent underlying disease. According to the final diagnoses, diseases that caused acute abdominal pain were classified into nine groups. RESULTS: The nine groups were group I "catastrophic surgical abdomen" (7 patients, 1.6%), group II "acute appendicitis and mesenteric lymphadenitis" (56 patients, 12.7%), group III "intestinal obstruction" (57 patients, 12.9%), group IV "viral and bacterial acute gastroenteritis" (90 patients, 20.4%), group V "peptic ulcer and gastroduodenitis" (66 patients, 14.9%), group VI "hepatobiliary and pancreatic disease" (14 patients, 3.2%), group VII "febrile viral illness and extraintestinal infection" (69 patients, 15.6%), group VIII "functional gastrointestinal disorder (acute manifestation)" (20 patients, 4.5%), and group IX "unclassified acute abdominal pain" (63 patients, 14.3%). Four patients were enrolled in two disease groups each. CONCLUSION: Patients were distributed unevenly across the nine groups of acute abdominal pain. In particular, the "unclassified abdominal pain" only group was not uncommon. Considering a systemic classification for acute abdominal pain may be helpful in the diagnostic approach in children.

Kawasaki Disease with Acute Respiratory Distress Syndrome after Intravenous Immunoglobulin Infusion / 대한구급학회지

Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. We report a case of KD with acute respiratory distress syndrome (ARDS) after intravenous immunoglobulin (IVIG) infusion. Lung manifestations associated with KD have previously been reported in the literature. Although IVIG infusion is an effective therapy for acute KD, there are some reported complications related to IVIG infusion: hypotension, aseptic meningitis, acute renal failure, hemolytic anemia, etc. The case of KD reported here was treated with IVIG and aspirin. A few days after recovery from KD, the patient developed fever and maculopapular rash. A diagnosis of relapse KD was made and retreated with IVIG infusion. However, the patient developed ARDS four days after the second IVIG infusion. The patient recovered from ARDS after nine days of ICU care, which included high frequency oscillation ventilation with inhaled nitric oxide, steroid treatment and other supportive care.

A case of Enterovirus 71 Infection Presented with Acute Flaccid Paralysis in Jeju Island / 대한소아신경학회지

Most human enterovirus 71 (EV71) infections present with mild conditions such as hand-foot-mouth disease or herpangina. However, EV71 can invade the central nervous system, causing neurologic diseases such as brainstem encephalitis, meningitis and acute flaccid paralysis despite the near complete eradication of polioviruses. Neurological complications from EV71 infection occur within a few days and can lead to death even though rare. There is no report for EV71 infection with severe neurological manifestation in Jeju Island so far. We therefore report a case of EV 71 infection with bilateral acute flaccid paralysis for the first time in Jeju Island with review of related articles.

Neurologic Complications of Bacterial Meningitis in Children / 대한소아신경학회지

PURPOSE: This study was performed to investigate clinical findings of acute neurologic complications and risk factors for chronic neurologic complications of bacterial meningitis in children. METHODS: Pediatric patients with community acquired bacterial meningitis diagnosed at Seoul National University Children's Hospital and Bundang Seoul National University Hospital were included. We investigated the relative frequency of neurologic complications and distribution of causative organisms. Chronic neurologic complication was defined as persistent neurologic deficit including recurrent seizures 6 months from the diagnosis. Multiple logistic regression analysis was used to identify risk factors for epilepsy and motor deficits, which were the most frequently reported chronic neurologic complications. RESULTS: A total of 90 cases were included in the study. Thirteen cases with less than 6 months follow-up duration were excluded from the analysis of risk factors for chronic neurologic complications. The mean age at diagnosis was 15.6 months. Streptococcus agalactiae was the most common pathogen accounting for 27 cases, followed by Streptococcus pneumoniae (19 cases), Hemophilus influenzae type b (13 cases), and Neisseria meningitidis (12 cases). Acute neurologic complications were found in 28 cases (31%): cerebral infarction in 16 cases, subdural effusion in 15 cases, and hydrocephalus in 9 cases. Chronic neurologic complications were found in 41 (53%) cases: epilepsy in 28 cases, motor deficit in 16 cases, hearing loss in 6 cases, and cognitive impairment in 4 cases. Cerebral infarction and S. pneumoniae infection were identified as risk factors for epilepsy. Cerebral infarction was a unique risk factor for motor deficit. CONCLUSION: Cerebral infarction is the important risk factor for the development of chronic neurologic complications including epilepsy and motor deficit in pediatric patients with bacterial meningitis.

Prognostic Indicators of Gross Motor Developmental Outcomes in Preterm Infants with Cerebral Insults as Detected by Neuroimaging / 대한소아신경학회지

PURPOSE: To examine the developmental outcome of preterm infants with cerebral insults and to evaluate the prognostic indicators for gross motor development. METHODS: Forty-eight preterm infants less than 37 weeks of gestation, who had been born at Seoul National University Bundang Hospital between March, 2004 and September, 2008 where the subjects of this. The infants' charts were reviewed to obtain data, including gestational age, birth weight, gender, 1/5 minute Apgar scores, neuroimaging findings, and others. RESULTS: Of the 48 patients, 29 infants (60.4%) were put into a normal developmental group and 19 (39.6%) were put into developmental delay group. Univariate analysis of the two groups showed that P values less than 0.05 were observed with respect to gestational age, premature rupture of membrane (PROM), respiratory distress syndrome, bronchopulmonary dysplasia, and patent ductus arteriosus. PROM and antenatal steroid showed statistically significant differences on a multivariate analysis. The same analysis method was applied to preterm infants less than a corrected age of 32 weeks. Multivariate analysis suggested that PROM showed statistically significant differences. Also, 48 patients were analyzed with respect to neuroimage finding. Twenty-five infants (52.1%) were assigned to a germinal matrix hemorrhage (GMH) group and 23 infants (47.9%) were allocated to a non-GMH group. Cesarean section delivery showed statistically significant difference according to univariate analysis. CONCLUSION: In preterm infants with cerebral insults, PROM and antenatal steroids were independent risk factors for impaired gross motor development.

A case of Rothmund-Thomson syndrome / 소아과

Rothmund-Thomson syndrome (RTS), is a rare autosomal recessive disorder, characterized by:skin photosensitivity, poikiloderma, sparse hair, sparse eyebrows/lashes, short stature, skeletal abnormalities, cataracts, and an increased risk of malignancy. Skeletal abnormalities include:dysplasia, absent or malformed bones, such as absent radii, osteopenia, and delayed bone formation. RTS is thought to result from chromosomal instability, and children with RTS are at risk of cancer. Reported cancers in children with RTS include:basal cell carcinoma, squamous cell carcinoma of the skin and osteosarcoma of bone. We report an 11 year-old boy, who presented to our institution with poikilodermatous skin change with telangiectasia and hyperpigmentation, absence of radius and thumb, and the development of osteosarcoma of the left tibia. The patient is now receiving supportive care and is receiving maintenance chemotherapy after surgery for osteosarcoma.

A Case of Neurofibromatosis Type 1 with Cortical Dysplasia / 대한소아신경학회지

Neurofibromatosis type 1(NF1) is the most common neurocutaneous syndrome which has an autosomal dominant pattern of inheritance. The NF1 gene is located on chromosome 17q11.2 and encodes for neurofibromin known as tumor suppressor protein. The disorder affects almost every organ and shows neurologic manifestations such as tumors, mental retardation and epilepsy. Epilepsy associated with NF1 occurs in about 4% and is known to have relatively good prognosis. Malformations of cortical development are less common in patients with NF1 than in other phakomatoses. To our knowledge, no report on NF1 with cortical dysplasia has been published in Korea. We report a child with NF1 associated with extensive cortical dysplasia, who presented initially infantile spasms and in the following months developed tonic seizures.

Merosin Deficient Congenital Muscular Dystrophy in Korea / 대한소아신경학회지

PURPOSES:Congenital muscular dystrophies(CMDs) are an autosomal recessive and heterogeneous disorders. The classic forms of CMD are subclassified into two major categories:merosin positive and deficient. Merosin deficient congenital muscualr dystrophy (MDCMD) is rare in Asia and it has never been reported especially in Korea. So, we summarized the clinical features with neuroimaging findings of the patients, who were diagnosed as MDCMD, for the first time in Korea. METHODS: Twenty three patients were diagnosed as CMD in Seoul National University Children's Hospital over 3 years(2001-2004). Among them, four patients with MDCMD were proven by merosin immunohistochemical staining. We reviewed their clinical, pathologic features, EMG/NCS findings and brain MRIs. RESULTS: Among 23 patients with CMD, 4 patients(17.4%) were MDCMD. All of them were presented at birth or early infancy with hypotonia, muscle weakness and joint contracture. They all could not walk and had myopathic faces, developmental delay, poor weight gain and scoliosis. EMG/NCS showed myopathic motor unit action potential (MUP) and decreased compound motor unit action potential(CMAP). Merosin deficiency was demonstrated in muscle or skin tissues. All of them had diffuse or focal high signal intensity lesions of white matter in brain MR T2WI. However, they showed neither mental retardation nor seizure though one of them had right occipital polymicrogyria. CONCLUSION: We reported 4 children with MDCMD for the first time in Korea. The prevalence in Korea might be lower than in Europe but probably higher than in Japan. If CMD patients have sustained delayed motor milestone with normal intelligence, myopathic face, decreased CMAP and myopathic MUP in EMG/NCS, MDCMD should be suspected and further diagnostic work up such as brain MR and merosin immunohistochemistry will be needed.

Clinical Characteristics of Neonatal Seizures / 대한소아신경학회지

PURPOSE: Neonatal seizures are major morbidities of various neurological insults in neonates and have the predictive value for neurodevelopmental outcome. Nevertheless, it is difficult to detect seizures in this period and to verify underlying causes. In this study, we investigated the clinical features of neonatal seizures and proved the role of brain MRI in detection of underlying neurological insults. METHODS:Twenty-four patients(M:F=7:17) with neonatal seizures are recruited among 1,157 neonates born between Mar. 2004 and Jan. 2005. Seizure types are classified based upon Volpe's criteria. Retrospective reviews of medical records and interictal electroencephalograms are performed. RESULTS:Subtle seizure is the most common seizure type(9 patients:37.5%). In 4 patients, two types of seizures are noted. Among 20 patients with brain ultrasound, thirteen patients show normal findings. In contrast, out of 16 patients with brain MRI, fourteen patients have abnormal findings. Among 13 patients with normal brain ultrasound, seven patients have abnormal findings in brain MRI. Abnormal background activities of interictal electroencephalograms are noted in twenty one patients(87.5%). Subsequent seizures are detected in 3 patients. CONCLUSION:Clinical features of neonatal seizures are variable, and more than two types of seizures can be noted in one patient. Background activity of the electroencephalogram may help in diagnosis of neonatal seizures and Brain MRI should be considered in detection of underlying cause.

Clinical Characteristics of Pediatric Multiple Sclerosis in Korea / 대한소아신경학회지

PURPOSE: Multiple sclerosis(MS) is an autoimmune demyelinating disorder causing significant neurological impairment in early adulthood. Since 1980, childhood MS has increased and the characteristics of childhood MS has been reported. For investigation of the clinical characteristics of childhood MS in Korea, we reviewed clinical presentations, paraclinical features, prognosis, and responses to interferone treatment of childhood MS patients. METHODS: We retrospectively reviewed the medical records of patients who have been diagnosed as MS according to McDonald criteria in Seoul National University Children's Hospital. 13 patients(M:F=6:7) were included in the study from 1988 to 2005. RESULTS: The age of onset was 1-12 years-old(mean 7.1) and the duration from initial presentation to 1st relapse was 3-27 months(mean 10.3). Initial presenting symptoms were motor disturbance, visual disturbance, bladder dysfunction, fever, brainstem dysfunction, headache and encephalitis-like-symptoms. All patients were treated with corticosteroids and 8 patients were on interferone-alpha treatment. EDSS score were 0-10(mean 1.8). CONCLUSION: The clinical characteristics of childhood MS were similar to the result from other studies in Korea, Japan, and eastern countries. Increasing number of childhood MS in Korea reflects the change of the environmental susceptibility to MS in Korean pediatric population. Interferone-alpha therapy can be considered as safe and effective treatment for modulating the clinical course of MS.