Characteristics of Meningitis with or without Enterovirus / 대한소아신경학회지

PURPOSE: Meningitis is an acute childhood infection caused by viral or bacterial infection. The purpose of the present study is to analyze the differences between enteroviral meningitis and non-enteroviral aseptic meningitis. METHODS: From January 2013 to December 2016, we retrospectively reviewed the medical records of a total of 303 aseptic meningitis patients who visited Wonju Severance Christian Hospital. We examined demographics of all patients and analyzed serologic and cerebrospinal fluid tests, clinical symptoms, and outcomes. RESULTS: Of a total of 303 patients, 197(65.0%) were male, and the most cases occurred from June to November (91.8%). The most common pathogen of meningitis was found to be enterovirus (65.0%). According to the etiology, the enteroviral meningitis group had significantly more headache and enteric symptoms (P=0.0003 and P=0.0013, respectively). Furthermore, the non-enteroviral meningitis group showed pleocytosis in the cerebrospinal fluid and a significantly higher rate of seizure at 1 to 4 years (P=0.0360 and P=0.0002, respectively). CONCLUSION: In this study, enteroviral meningitis was the most common and the prognosis was good. When compared between two groups, neurological symptoms were frequent in patients with non-enteroviral meningitis in groups 1 to 4 years.

Primary central nervous system anaplastic large cell lymphoma presenting initially with meningitis

Primary or secondary anaplastic large-cell lymphoma (ALCL) is an uncommon type of T-cell lymphoma and is extremely rare.1-3 It was said that only 15-20 cases of primary CNS-ALCLs have been reported in the literature.3 ALCL may present with a variety of symptoms and MRI findings. We report a case of a 10-year-old girl who presented with meningitis and later developed optic neuritis. She was initially diagnosed as tuberculosis meningitis after a positive interferon-γ test. Clinicians should be

Interleukin-21 Receptor Gene Polymorphisms in Kawasaki Disease

BACKGROUND AND OBJECTIVES: Interleukin-21 receptor (IL-21R) gene polymorphism is related with the development of systemic vasculitis. In this study, we investigated the polymorphisms of IL-21R gene in patients with Kawasaki disease (KD). SUBJECTS AND METHODS: We genotyped the promoter region of IL-21R gene (-2500 bp to +1 bp) in 100 patients with KD and 100 healthy controls. All study subjects were Korean. We designed five pairs of primers and performed polymerase chain reaction (PCR) and direct sequencing. We analyzed whole promoter sequences of 200 individuals with comparison to reference sequences of IL-21R gene (NG_012222.1/NC_000016.9). RESULTS: We found five single nucleotide polymorphisms (SNPs) of which minor allele frequency (MAF) >0.01 in the promoter region of IL-21R gene. Those are -1681 G>T (chromosome site 27411802), -379 G>A (27413104), -332 G>C (27413151, rs2214537), -237 A>T (27413246), and -53 G>A (27413430). There is no significant difference in MAF of each SNP between patients with KD and healthy controls except -237 A>T. Twenty five patients with KD had more than 1 SNP in contrast to only seven healthy controls had. The patients with KD have significantly more IL-21R gene polymorphisms than controls (odds ratio: 3.0, 95% confidence interval: 1.6-5.6, p=0.0005). There was no significant correlation between IL-21R gene polymorphisms and the serum level of IL-21. The serum level of total IgE was not significantly correlated with the presence of IL-21R gene polymorphisms. CONCLUSION: Our data suggest that the genetic susceptibility profile for KD may include IL-21R gene.

Elevated Serum Levels of IL-21 in Kawasaki Disease

PURPOSE: The serum level of immunoglobulin (Ig)E has been reported to be elevated in patients with Kawasaki disease (KD). We investigated whether interleukin (IL)-21, rather than IL-4, could be related to elevated serum levels of IgE in KD. METHODS: Sera from 48 patients with KD and 12 controls with high fever were collected to determine the level of IgE using an immunoassay system and the levels of IL-4 and IL-21 were determined using enzyme-linked immunosorbent assay kits. RESULTS: The median IL-21 level of KD patients was significantly elevated, at 499.5 pg/mL (range: <62.5-1,544 pg/mL), whereas that of controls was <62.5 pg/mL (<62.5-825 pg/mL; P<0.001). The median IL-4 level of KD patients was not elevated (4.0 pg/mL; 2.1-7.6 pg/mL). The median level of total IgE in KD patients was 58.0 IU/mL (5-1,109 IU/mL). No statistically significant correlation was found between IL-21 and total IgE levels (Spearman's R=0.2; P=0.19). CONCLUSIONS: Patients with KD have elevated levels of IL-21 in the serum. IL-21 may play a role in the pathogenesis of KD.

The Association of Lymphopenia with the Clinical Severity in the Korean Children Admitted to the Hospital with Pandemic (H1N1) 2009 Infection / 감염과화학요법

BACKGROUND: Critical illness due to pandemic (H1N1) 2009 is an emerging threat to global health. In this study, lymphopenia was focused on as a major risk factor for a critical clinical course of pandemic (H1N1) 2009 infection. We investigated the association of lymphopenia at the time of admission with the clinical severity of the admitted children with pandemic (H1N1) 2009 infection. Material and Methods: We performed a retrospective study on the patients who were younger than 15 years of age and who were admitted to Wonju Christian Hospital due to pandemic (H1N1) 2009 infection between August 20, 2009 and February 20, 2010. Pandemic (H1N1) 2009 infection was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) in all patients. We divided the study period into two periods as August 20 - November 30 2009 (pre-vaccination period) and December 1 2009 - February 20 2010 (post-vaccination period). The clinical differences between two periods were analyzed. To define the role of lymphopenia, we examined the differences of clinical manifestations between the H1N1 patients with lymphopenia and those without lymphopenia. RESULTS: Among the 2,399 children who had H1N1 infection, 149 patients (6.2%) were admitted under the following diagnoses: pneumonia (67.1%), bronchiolitis/asthma (18.8%), croup (6%) and febrile convulsion (8.7%). The median age of the patients was significantly different between during the pre-vaccination period and the post-vaccination period (6 years of age [range: 0.25-14] vs. 3 years of age, [range: 0.1-14], P<0.05). The proportion of patients who had lymphopenia was significantly different between two periods (39.5% vs. 20%, P<0.05). When we compared the clinical severity between the patients with lymphopenia and those without lymphopenia, age (P<0.0001), the length of hospital stay (P<0.0001) and the serum levels of C-reactive protein (P<0.01) were significantly different. CONCLUSION: Our data support that lymphopenia may be a major determining factor that could cause a critical clinical course during pandemic period among children in the Republic of Korea.

Predicting Factors for Refractory Kawasaki Disease

BACKGROUND AND OBJECTIVES: About 10-15% of Kawasaki disease (KD) is refractory to intravenous immunoglobulin (IVIG) therapy. This study was designed to investigate the predicting factors for refractory KD. SUBJECTS AND METHODS: We reviewed retrospectively the clinical records of 77 patients with typical KD admitted at Wonju Christian Hospital from January, 2005, to December, 2008. The variance of laboratory and demographic parameters between the IVIG-responsive group and IVIG-resistant group were analyzed. Thirteen patients with urinary tract infections were randomly collected as a febrile control group. RESULTS: Among 77 patients diagnosed with complete KD, 13 patients (16.9%) were IVIG-resistant. The febrile period and hospital days were significantly longer in the IVIG-resistant group than IVIG-responsive group (p<0.001, p=0.002). Serum levels of albumin and sodium were significantly lower in the IVIG-resistant group (p=0.025). The Kobayashi score could differentiate these two groups (p=0.015). Fewer lymphocytes was observed during the subacute phase in the IVIG-resistant group (p=0.032). Coronary arterial dilatations (CADs) were observed in 10.9% (7/64) of IVIG-responders and 38.5% (5/13) of IVIG-resistant patients (p=0.038). CONCLUSION: The percentage of neutrophils and lymphocytes in patients with KD, in addition to known risk factors for refractory KD, may help predict IVIG-resistance in patients with KD.

Relationship Between Gallbladder Distension and Lipid Profiles in Kawasaki Disease

BACKGROUND AND OBJECTIVES: Kawasaki disease (KD) is an acute systemic vasculitis in children which causes coronary arterial dilatation (CAD) and gallbladder distension (GBD). There is a dearth of investigating the relationship between the severity of KD and GBD with lipid profiles. SUBJECTS AND METHODS: A total of 80 patients with 'complete KD' who were diagnosed from January 2005 to May 2009 was enrolled in this study. Serum cholesterol {total, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C)}, triglyceride (TG), complete blood count, inflammation markers {erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)} were measured at the time of admission during febrile period. Echocardiography and abdominal sonogram were performed in all patients to determine CAD and gallbladder size. According to GBD, patients with KD were classified as patients with GBD and patients without GBD. Between two groups, demographic and clinical data were analyzed. RESULTS: The serum level of LDL-C was significantly lower in patients with GBD (p=0.03) compared with patients without GBD or febrile control. There was no significant difference in inflammatory indices between patients with GBD and patients without GBD. GBD was not significant risk factor of CAD in this study (odds ratio=2.0, 95% confidence interval=0.82-5.3, p=0.16). CONCLUSION: This is the first study that highlights the relationship between the GBD and lipid metabolism in patients with KD. This study provides clinical insights about potential mechanism underpinning the relationship between the GBD and lipid metabolism.

A Tapping the usefulness of Whole Blood Interferon-gamma Assay for Diagnosing Tuberculosis Infection in Children / 결핵및호흡기질환

BACKGROUND: QuantiFERON(R)-TB Gold In Tube (QFT-G IT) has been used for diagnosing latent tuberculosis infection and active tuberculosis (TB) since 2007. However, there has not been enough data on QFT-G IT for universal use in children. In this study, we evaluated the clinical usefulness of the QFT-G IT in pediatric practice. METHODS: We retrospectively reviewed the clinical records of 70 patients younger than 18 years of age who had taken QFT-G IT and had a tuberculin skin test (TST) between July 2007 and July 2009 at Wonju Christian Hospital. The subjects were divided into two groups, asymptomatic TB exposure group and disease group. Four patients who were taking immunosuppressants during the study period were excluded. RESULTS: A total of 66 immunocompetent children were included in this study. Among 27 asymptomatic children who had contact histories of TB, 6 (22.2%) were found to be positive by QFT-G IT. Eleven (40.7%) and 5 (18.5%) children were found to be positive by TST with cutoff values of > or =5 mm and > or =10 mm, respectively. Agreement was fair to good between QFT-G IT and TST (kappa=0.59: cutoff value > or =5 mm, kappa=0.7: cutoff value > or =10 mm). In disease group, 14 patients (35.9%) were diagnosed with active tuberculosis, 8/14 (57.1%) were positive on TST and 9/14 (64.3%) on QFT-G IT. The positive rate of acid-fast bacilli smear, TB-polymerase chain reaction, and culture for tuberculosis was 11% (1/9), 27.3% (3/11) and 33.3% (3/9), respectively. CONCLUSION: Our data support that the QFT-G IT can be used as an additional diagnostic tool for latent and active tuberculosis infection in children.

Group A beta-hemolytic Streptococcal Meningoencephalitis with Unilateral Hemiparesis / 소아감염

Group A streptococcus (GAS) rarely causes meningoencephalitis in children without risk factors. A previously healthy 8 year-old child presented with lethargy, high fever, and vomiting. The clinical course was unusual including intractable seizures, disseminated intravascular coagulation (DIC), and left hemiparesis in spite of the appropriate and timely administration of antibiotics and corticosteroids. The microbiologic studies revealed that the pathogen was susceptible to penicillin and GAS M18 strains. This case showed the importance of the GAS vaccine in addition to appropriate antibiotics.

Febrile Seizures and Benign Convulsion with Mild Gastroenteritis in Children / 대한소아신경학회지

PURPOSE: Febrile Seizures and Benign convulsion with mild gastroenteritis(BCwMG) are common neurological disorders in children. We would like to know the clinical characteristics and prognosis of febrile seizure associated with acute gastroenteritis(A), BCwMG(B) and febrile seizure associated with a febrile illness not caused by acute gastroenteritis(C) in children. METHODS: We reviewed the medical records of 569 pediatric patients aged from 3 months to 5 years that admitted to the Wonju Christian Hospital from 2004 to 2007 for febrile seizures or BCwMG. RESULTS: The mean ages were A; 1.51+/-1.10 years, B; 1.14+/-0.44 years, C; 1.84+/-1.33 years. The most common seizure type was generalized seizure(95.4%). The average frequency of seizure was higher in B than A and C(A; 1.53+/-0.88, B; 2.12+/-1.35, C; 1.23+/-1.11 times/day, P<0.001). The incidence of positive parents history for febrile seizures was higher in A and C compared to B(A; 14.5%, B; 4.3%, C; 17.8%, P<0.05). The mean WBC count in peripheral blood was higher in C than A and B(A; 10,532+/-5,151, B; 8,686+/-3,053, C; 12,932+/-5,866 mmol/L, P<0.001). The positive rate of stool rotavirus antigen test was higher in A and B compared to C(A: 45.7%, B: 42.6%, C: 14.5%, P<0.05). But there were no statistically significant differences of sex ratio, duration of seizures, serum sodium level, abnormal neurodevelopmental status, rate of EEG and neuroimaging abnormalities among three groups. The recurrence rate of febrile seizure after the 1st seizure was A; 9.1%, B; 5.8%, C; 11.9% and unprovoked seizure was A; 5.4%, B; 1.4%, C; 1.6%. CONCLUSION: We consider prophylactic short term management of recurrent episodes of seizures within 24 hours, especially in febrile seizure associated with acute gastroenteritis and BCwMG. Also, It will be necessary to educate parents about the possibility of recurrence of febrile seizures or unprovoked seizures, although the risk is low.

Sleep disorders in childhood / 소아과

Sleep disorders are very common among pediatric patients. Its prevalence is between 10% and 45% in preschool- and school-aged children. However parents commonly do not concern about their children's sleeping habits and for many pediatricians, there is not part of the routine office visit about a childs sleep. Sleep disorders were classified by International Classification of Sleep Disorder (ICSD) as dyssomnias, parasomnias, sleep disorders associated with mental, neurologic, or other medical disorders, and proposed sleep disorders. There are lots of differences in the causes, manifestations, and managements of sleep disorders between children and adults. The sleep disorders in childhood may manifest themselves as bedtime resistance, refusal to go to bed at a parentally described time, sleep-onset delay, inability to fall asleep within a reasonable time, prolonged nighttime awakening, and inability to return to sleep without assistance after waking during the night, and so have wide-ranging influences on children's behavior, mood, school performance, and family life. It's very important for pediatrician to concern about the sleep disturbances in childhood and so the problems of sleep in children should be early detected and managed.

A Case of Partial Trisomy 9p Syndrome with 3-Ketothiolase Deficiency / 대한소아신경학회지

Trisomy 9p syndrome was first described by Rethore et al in 1970 and about 150 cases have been reported. The characteristic features of the partial trisomy 9p syndrome is clearly recognizable faces, which include microcephaly, facial deformities, skeletal and dermatoglyphic anomalies with variable degrees of mental retardation. The 3-ketothiolase deficiency was first described in 1971 and about 30 cases have been reported. The 3-ketothiolase deficeiency is an inborn error of isoleucine and ketone body catabolism that shows autosomal recessive traits, caused by a deficiency of mitochondrial acetoacetyl-coenzyme A thiolase(T2). We report a case of partial trisomy 9p syndrome with 3-ketothiolase deficeiency in a 4-years-old female. The karyotype of the patient was confirmed as 46,XY, add(9)(p23) mat. In the urine organic acid test, 3-ketothiolase deficiency was reported.

Comparative Study of Febrile or Benign Seizures Associated with Acute Gastroenteritis / 대한소아신경학회지

PURPOSE:Acute gastroenteritis is one of the causes of febrile seizures or benign seizures in children. This study was performed to find out the clinical characteristics and the prognosis of convulsions by acute gastroenteritis. METHODS:From January 2000 to December 2004, sixty five pediatric patients who suffered from convulsions due to acute gastroenteritis were classified into benign seizures (n=36) or febrile seizures(n=29) in Wonju Christian Hospital, Wonju College of Medicine, Yonsei University. We compared the age of onset, sex, the frequency and the duration of convulsions, blood electrolytes and peripheral white blood cell counts, findings of the cerebrospinal fluid examination, and the electroencephalograms between the two groups. In addition, we retrospectively analyzed their recurrence of convulsive diseases for 7 to 59 months after the first attacks. RESULTS:There was no difference of onset age, frequency and duration of convulsion between the two groups(P=0.12, P=0.83 and P=0.08). The types of convulsions were generalized seizures in both groups. There were 16 cases of positive responses to the antigen tests for stool rotavirus, and 12 of them(75%) belonged to the benign seizure group. And other laboratory findings were normal. During the follow-up period, 4 patients(11.1%) in the benign seizure group experienced febrile seizures, 2 patients(5.6%) benign seizures and 1 patient a generalized tonic-clonic seizure, whereas 3 patients(10.3%) in the febrile seizure group experienced simple febrile seizures. CONCLUSION:The comparative analysis between the benign seizure and the febrile seizure groups revealed no significant differences on the clinical characteristics except the number of positive responses to the rotavirus antigen tests in stool. And the recurrence rates of convulsions in both groups were similar with previous studies which showed no significant differences between the two groups.

A Case of Moyamoya Disease with Neurofibromatosis Type I / 소아과

Neurofibromatosis type I is an autosomal dominant disorder with varied manifestations in bone, soft tissue, the nervous system and skin. This is characterized by cafe-au-lait spots, neurofibromas, Lisch nodules, optic glioma, bony displasia, and intertriginous freckling. One of the more serious aspect of the disease relates to the arterial involvement. Vascular changes in neurofibromatosis may occur in any arterial tree from the proximal aorta to the small arteries but these changes are most common in the renal arteries, aorta, celiac arteries and mesenteric arteries. Of the many complications observed in neurofibromatosis type I, cerebrovascular lesions may be the least appreciated. About 40 cases of neurofibromatosis type I associated with occlusive cerebrovascular disorders have been reported in the literature, but MRI and angiographic findings typical of moyamoya disease are rarely described. We experienced a case of moyamoya disease associated with neurofibromatosis type I in a 3-year-old girl who of complained gait disturbance and paraparesis and showed findings typical of moyamoya disease on MRI and carotid angiogram.

Bronchiolitis Obliterans Associated with Stevens-Johnson Syndrome / 소아과

Bronchiolitis Obliterans(BO) is one of the rare inflammatory lung disease that primarily affects bronchi and bronchioles, followed by partial or complete obstruction. In children, the etiology of BO has been under consideration, but infections and toxic inhalation, connective tissue diseases, lung transplantation, congestive pulmonary edema, etc., may be causes of BO. Even though steroid therapy was reported as an effective treatment, there are few data regarding the epidemiology, pathophysiology, long term prognosis and therapy. Here we describe a 5-year-old boy who presented with intractable wheezing associated with Stevens-Johnson syndrome after Varicella-Zoster virus infection and was diagnosed as BO through chest high-resolution computed tomography.

Intrahepatic Arterio-Venous Shunts in a Patient with Hypergalactosemia Detected by Neonatal Screening

We report a case of 15 days old newborn presenting with hypergalactosemia detected by newborn screening who had intrahepatic arterio-venous shunts with multiple pin-head sized cutaneous hemangiomas. Plasma level of galactose was elevated to 11.3 mg/dL at age of 7 days, but the activity of galactose-metabolizing enzymes including galactose-1- phosphate uridyltransferase, galactokinase, and uridine diphosphate galactose-4-epimerase were all normal. Intrahepatic arterio-venous shunts were diagnosed by abdominal ultrasonography with color doppler ultrasonography and abdominal computed tomography. At age of 3 months, the plasma level of galactose further elevated to 14.73 mg/dL, at which time lactose-free cows milk formula was started. At age of 6 months, the plasma level of galactose decreased to within normal range with disappearance of previously noted multiple cutaneous hemangiomas. In hypergalactosemia of the newborn, the intrahepatic shunts should be considered as a possible cause, once hereditary enzyme deficiencies have been ruled out.

The Incidence and Risk Factors of Posttraumatic Seizure in Children / 소아과

PURPOSE: The goal of our study was to identify the incidence and clinical, neurophysiological and neuroradiological variables with predictive value for posttraumatic seizure(PTS). METHODS: The medical records of 625 children with head traumas under 15-year-old who were admitted to the Wonju Christian Hospital, from January, 1993 to January, 2002 were retrospectively reviewed. Among them, 472 patients were included in this study. The PTS patients were divided into early PTS, in whom seizure occurred within one week after head trauma and late PTS, in whom seizure occurred beyond the first week after head trauma. The injuries were classified into mild(Glasgow Coma Scale, GCS 13 to 15 or no brain CT abnormality and a brief hospital stay), moderate(GCS, 9 to 12, or a GCS above 12 and longer than 48-hour hospital stay, or brain CT abnormalites) and severe(GCS, below 9). The variables such as age, sex, duration of unconsciousness, GCS, brain CT scan finding, initial neurologic finding and anticonvulsant therapy were analyzed for risk factors of PTS. RESULTS: Early PTS was developed in 41(8.7%) patients, 35(77.8%) patients among them had a seizure within 24 hours after head trauma. Late PTS was developed in 17(3.6%) patients. The frequency and duration of PTS were not correlated with the latency of PTS. And there was correlation between the frequency and duration of PTS. The 82.9% of early PTS and the 76.5% of late PTS were generalized tonic-clonic seizure. There was a significant difference in the incidence of PTS by severity of head trauma. The incidence of PTS after mild head trauma(5.8%) was lower than after severe head trauma(29.9%). The risk factors of early PTS were unilateral hemorrhage, neurologic finding(hemiparesis and coma), GCS(under 12 score), and diffuse contusion. And the late PTS were the same as early PTS, except for diffuse contusion, and age factor(under 2 years was also significant). CONCLUSION: The incidence and risk factors of PTS were correlated with severity of head trauma.

The Evidence of Epileptic Seizure-induced Neuronal Injury by Animal Study

No abstract available.

A Case of Intracerebral Thrombosis and Cortical Hemorrhage Complicated by Streptococcus pneumoniae Meningitis / 대한소아신경학회지

Streptococcus pneumoniae is the most common pathogen of bacterial meningitis in childhood. It causes such intracranial complications as hydrocephalus, cerebral edema, inappropriate secretion of antidiuretic hormone(SIADH), and convulsion, and also such cerebral vascular complications as vasculitis, thrombosis, aneurysm, infarction, and subarachnoid hemorrhage. We report a male of 4 months old who had intracerebral cortical hemorrhage and sinovenous thrombosis complicated by streptococcus pneumoniae meningitis. Also, we reviewed the literature on intracerebral vascular complications related to bacterial meningitis.

A Case of Distal 10q Partial Trisomy Syndrome / 대한소아신경학회지

Since Yunis and Sanchez described in 1974, distal 10q partial trisomy has been recognised as a chromosomal anomaly, which has typical features, psychomotor delays, distinctive dysmorphic appearance and growth retardation. Also, it is associated with cardiac, renal and ocular anomalies. Most of them result from an unbalanced tanslocation or a deletion but, pure duplications are very rare. We report a 19-month-old boy with typical clinical features of distal 10q partial trisomy with a pure duplicatin of 10q.