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.

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.

Probiotic mixture reduces gut inflammation and microbial dysbiosis in children with atopic dermatitis.

BACKGROUND: Recent data suggested that dysbiosis of the gut microbiome is associated with childhood allergic diseases. Oral administration of probiotic formulations may improve the severity of atopic dermatitis (AD) by restoring imbalanced gut microbiota and reducing intestinal inflammation in children. OBJECTIVES: The aim of this study was to investigate the effects of a probiotic mixture on the clinical severity of AD, gut inflammatory markers and alterations in microbiome dysbiosis in children with AD. METHODS: A total of 25 subjects were enrolled in this study and administered with a mixture of probiotic strains consisting of Lactobacilli and Bifidobacteria for 4 weeks. The clinical efficacy of the probiotic mixture was assessed using SCORAD index and TEWL. Faecal calprotectin levels were measured as a marker for intestinal inflammation. The composition and diversity of the gut microbiome were analysed using 16S rRNA pyrosequencing. RESULTS: The SCORAD (38.9 ± 17.2 vs 29.0 ± 15.4, P < 0.001) and TEWL (58.3 ± 12.5 vs 27.3 ± 8.7 g/m2 /h, P = 0.028) were significantly decreased after 4 weeks administration of the probiotic mixture. The faecal calprotectin level (121.5 [27.7-292.9] vs 37.0 µg/g [12.6-108.9 µg/g], P = 0.038) was significantly decreased. The α-diversity and composition of the gut microbiome were not significantly changed, but ß-diversity was increased after 4 weeks. CONCLUSIONS: The oral administration of the probiotic mixture was effective in reducing clinical severity and intestinal inflammation in children with AD. Gut microbial diversity was slightly increased after administration of the probiotic mixture. The results of this study suggest that a probiotic mixture can alleviate AD by decreasing inflammation and modulating the gut microbiota in children with AD.

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.

Clinical outcomes of pediatric Anti-NMDA receptor encephalitis.

OBJECTIVE: To investigate the clinical features and long-term outcomes of pediatric Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: Thirty-two anti-NMDAR encephalitis patients with positive anti-NMDAR antibody test results were recruited. Clinical outcomes were evaluated using the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) and the modified Rankin Scale (mRS). RESULTS: The median age of onset was 9.0 years (range, 0.7-17.2 years). Twenty-four patients (75.0%) were female. All patients received first-line immunotherapy including intravenous immunoglobulin and/or steroid therapy. The second-line immunotherapy was administered to 22 patients (68.8%). Clinical outcomes were evaluated in 27 patients who were followed for longer than 6 months after onset, among whom the median follow-up duration was 31.2 months (range, 6.3-82.9 months). The proportion of patients with ≤2 points on the mRS at their 12-month follow-up was 79.2% (19/24). The CASE scores of these 19 patients ranged from 0 to 5, with language and memory deficits accounting for most of these disabilities. When the outcome was assessed according to onset age (<12 years or 12-18 years), the younger group tended to show a slower recovery over their clinical course. CONCLUSIONS: Despite overall favorable clinical outcomes, mild cognitive problems, including language and memory, may persist in pediatric anti-NMDAR encephalitis patients. A specific outcome measure, such as CASE, should be adopted to delineate clinical outcomes and aid the development of individualized treatment plans.

Can moderate-intensity aerobic exercise ameliorate atopic dermatitis?

It has been shown that aerobic exercise improves atopic dermatitis (AD), although the mechanism is not clear. Here, we propose a hypothesis that moderate-intensity aerobic exercise improves AD in a mouse model through modulating allergic inflammation. The DNCB-treated mouse model for eczema was divided into 3 groups: (a) not subjected to aerobic exercise, (b) subjected to continuous aerobic exercise and (c) subjected to accumulated aerobic exercise. After given exercise using a treadmill device either 30 min/d or 10 min × 3/day at a speed of 16 m/min, for 9 days, respectively, dermatitis symptom score, thickness of epidermis/dermis and eosinophil infiltration were decreased in the 2 exercise groups compared to the sedentary living group. The serum levels of IgE, MCP-1 and MDC showed a significant decrease both in the continuous or accumulated exercise groups. Moderate-intensity aerobic exercise ameliorates dermatitis symptoms through immune modulation in the DNCB-treated mouse model for eczema.

Correlation of serum interleukin-31 with pruritus and blood eosinophil markers in children with atopic dermatitis.

Background: Atopic dermatitis (AD) is chronic pruritic inflammatory skin disease in children. Interleukin (IL) 31 is a recently discovered cytokine associated with chronic skin inflammation and pruritus. Objectives: The aims of this study were to determine whether serum IL-31 levels are increased in children with AD and to examine the relationship between IL-31 and other clinical biomarkers in AD. Methods: Serum cytokine levels, including IL-31, IL-4, and IL-12, were measured in 38 patients with AD and 10 healthy children. Peripheral blood eosinophils, serum immunoglobulin E levels, eosinophil cationic protein, and thymic stromal lymphopoietin (TSLP) were measured. We also estimated the clinical severity of AD by using the Scoring Atopic Dermatitis (SCORAD) index by a single clinician. Results: The serum IL-31 levels were significantly higher in the patients with AD than in the healthy children. IL-31 correlated well with the SCORAD index and blood eosinophilic inflammatory markers. The serum level of TSLP was also higher in patients with AD than in the healthy children; however, levels of IL-4 and IL-12 were not different between AD and healthy children. There was no significant difference in serum IL-31 levels between patients with atopic AD and nonatopic AD. Conclusion: This study showed that serum IL-31 levels were significantly elevated in patients with AD than in the healthy children and correlated well with disease severity. IL-31 seemed to be one of the cytokines that induce pruritus and eosinophilic inflammation in AD. Serum IL-31 correlated with pruritic symptoms and disease course of AD.

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.

Prevalence, Incidence, and Recurrence of Febrile Seizures in Korean Children Based on National Registry Data.

BACKGROUND AND PURPOSE: Febrile seizures (FS) are the most common type of seizure during childhood, reportedly occurring in 2-5% of children aged 6 months to 5 years. However, there are no national data on the prevalence of FS in Korea. This study determined the prevalence, incidence, and recurrence rates of FS in Korean children using national registry data. METHODS: The data were collected from the Korea National Health Insurance Review and Assessment Service for 2009-2013. Patients with febrile convulsion as their main diagnosis were enrolled. The overall prevalence of FS in more than 2 million children younger than 5 years was estimated, and the incidence and recurrence rates of FS were determined for children born in 2009. RESULTS: The average prevalence of FS in children younger than 5 years based on hospital visit rates in Korea was 6.92% (7.67% for boys and 6.12% for girls). The prevalence peaked in the second to third years of life, at 27.51%. The incidence of FS in children younger than 5 years (mean 4.5 years) was 5.49% (5.89% for boys and 5.06% for girls). The risk of first FS was highest in the second year of life. The overall recurrence rate was 13.04% (13.81% for boys and 12.09% for girls), and a third episode of FS occurred in 3.35%. CONCLUSIONS: Our study determined the overall prevalence of FS using data for the total population in Korea. The prevalence was comparable to that reported for other countries. Patients with three episodes of FS need to be monitored carefully.

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.

Elevated fecal calprotectin levels are associated with severity of atopic dermatitis in children.

BACKGROUND: Recent data suggested that imbalance in gut microbiota and gastrointestinal inflammation are associated with the childhood allergic disease. Fecal calprotectin has been used for a non-invasive marker of gut inflammation. OBJECTIVE: The aim of this study was to investigate the relationships between fecal calprotectin level and the clinical severity of atopic dermatitis (AD) in children. METHODS: We enrolled 65 subjects with AD. The concentration of calprotectin was measured in each subject's fecal sample. RESULTS: The geometric mean fecal calprotectin level of the total subjects was 33.1(10.1-108.9) µg/g. Among the 65 subjects, 44(67.7%) showed calprotectin levels lower than 50µg/g(Group 1), and 21(32.3%) were higher than 50µg/g(Group 2). The mean SCORAD index was significantly higher in Group 2 than Group 1(31.0±16.0 vs 22.2±15.3, p=0.046). The geometric mean serum total IgE levels was higher in Group 2 compared to Group 1(361.4[31.6-992.3]IU/mL vs 175.9[44.3-699.2]IU/mL, p=0.040). The mean blood eosinophils were significantly higher in Group 2 than in Group 1(497.7[239.8-1032.8]/µL vs 281.5[121.5-652.0]/µL, p=0.034). The incidence of exposure to environmental tobacco smoke was significantly higher in Group 2 compared to Group 1(76.2% vs 47.7%, p=0.036). Geometric mean fecal calprotectin level in severe AD was significantly higher than that of mild-to-moderate AD(66.7[13.5-330.3]µg/g vs 29.4[10.1-85.6]µg/g, p=0.044). The fecal calprotectin level significantly correlated with the SCORAD index(r=0.303, p=0.014). CONCLUSIONS: Higher fecal calprotectin levels were observed in subjects with severe AD. Elevated fecal calprotectin level as a gastrointestinal inflammatory marker may associate with childhood AD. Measurement of fecal calprotectin might be useful for assessment of severity of childhood AD.

Association Between Sensitization to Mold and Impaired Pulmonary Function in Children With Asthma.

PURPOSE: Recent data indicate that sensitization to mold contributes to the severity and persistence of asthma. In this study, we investigated the relationships between sensitization to mold and lung function parameters in children with asthma. METHODS: We retrospectively reviewed clinical data from 551 asthmatic subjects. We selected subjects who met clinical diagnostic criteria of asthma. Their spirometry, methacholine challenge tests, and measurements of blood eosinophils, serum IgE, eosinophil cationic protein (ECP) and fractional exhaled nitric oxide (FeNO) results were included. Skin prick testing (SPT) results with 13 common aeroallergens in Korea including house dust mites, animal dander, pollen, cockroach and mold were reviewed. Subjects were divided into 3 groups according to their SPT results. Subjects who showed no positive result to any aeroallergen were designated as group 1 (non-sensitized). Group 2 represented subjects who were sensitized to aeroallergens other than mold (other allergen-sensitized) and group 3 included subjects who were sensitized to mold allergens (mold-sensitized). RESULTS: Among the 551 asthmatic subjects, 67 (12.2%) were sensitized to mold and 366 (66.4%) were sensitized to other aeroallergens. The log mean IgE levels were higher in groups 2 (5.96±1.14 IU/mL) and 3 (5.81±0.97 IU/mL) compared to group 1 (3.88±1.68 IU/mL). Blood eosinophils, ECP and FeNO concentrations were significantly higher in groups 2 and 3, but no significant difference was found between the 2 groups. The mean FEV1 value was significantly lower in group 3 (86.9±12.1%pred) than in groups 2 (92.0±14.8%pred) and 1 (93.4±15.4%pred). The log mean methacholine PC20 was significantly lower in group 3 (0.08±1.91 mg/mL) than in groups 2 (1.31±1.69 mg/mL) and 1 (2.29±1.66 mg/mL). CONCLUSIONS: We observed a differential association between mold and other aeroallergen sensitization, and severity of asthma. Sensitization to mold is associated with lower lung function and increased airway hyper-responsiveness in children with asthma. Mold sensitization could be an important factor determining asthma severity particularly airflow limitation in children.

Neuroprotective Effect of Lacosamide on Hypoxic-Ischemic Brain Injury in Neonatal Rats.

BACKGROUND AND PURPOSE: Lacosamide (LCM) is an antiepileptic drug that enhances the slow inactivation of sodium channels and modulates collapsin response mediator protein-2. LCM was recently demonstrated to exert a neuroprotective effect in a murine model of traumatic brain injury and status epilepticus. Assuming the same underlying excitotoxicity-related brain injury mechanism, we hypothesized that LCM would have a neuroprotective effect in hypoxic-ischemic brain injury. METHODS: We divided rats into three groups at each testing session: pre- or postfed with LCM, fed with normal saline, and sham. A hypoxic-ischemic brain injury was induced by subjecting 7-day-old rats to right carotid artery coagulation followed by 2.5 h of exposure to 8% oxygen. The animals were killed on postnatal day 12 to evaluate the severity of brain damage. Open field testing was also performed between week 2 and week 6, and the Morris water maze test was performed in week 7 after hypoxia-ischemia. RESULTS: The incidence of liquefactive cerebral infarction was lower in rats prefed with LCM at 100 mg/kg/dose, with the mortality rate being higher at higher doses (200 and 300 mg/kg/dose). The infarct areas were smaller in LCM-prefed rats in several brain regions including the hemisphere, hippocampus, cortex, and striatum. Spatial learning and memory function were better in LCM-prefed rats (p<0.05). No effect was observed in postfed rats. CONCLUSIONS: This study suggests that LCM pretreatment exerts a neuroprotective effect on hypoxia-ischemia in neonatal rats. The obtained results suggest that LCM pretreatment could be used as an effective neuroprotective method for neonates under hypoxic-ischemic conditions including heart surgery.

Consecutive analysis of mutation spectrum in the dystrophin gene of 507 Korean boys with Duchenne/Becker muscular dystrophy in a single center.

INTRODUCTION: Duchenne and Becker muscular dystrophies (DMD and BMD) are allelic X-linked recessive muscle diseases caused by mutations in the large and complex dystrophin gene. METHODS: We analyzed the dystrophin gene in 507 Korean DMD/BMD patients by multiple ligation-dependent probe amplification and direct sequencing. RESULTS: Overall, 117 different deletions, 48 duplications, and 90 pathogenic sequence variations, including 30 novel variations, were identified. Deletions and duplications accounted for 65.4% and 13.3% of Korean dystrophinopathy, respectively, suggesting that the incidence of large rearrangements in dystrophin is similar among different ethnic groups. We also detected sequence variations in >100 probands. The small variations were dispersed across the whole gene, and 12.3% were nonsense mutations. CONCLUSIONS: Precise genetic characterization in patients with DMD/BMD is timely and important for implementing nationwide registration systems and future molecular therapeutic trials in Korea and globally. Muscle Nerve 55: 727-734, 2017.

Application of genetically engineered Salmonella typhimurium for interferon-gamma-induced therapy against melanoma.

Salmonella have been experimentally used as anti-cancer agents, because they show selective growth in tumours. In this study, we genetically modified attenuated Salmonella typhimurium to express and secrete interferon-gamma (IFN-γ) as a tumouricidal agent to enhance the therapeutic efficacy of Salmonella. IFN-γ was fused to the N-terminal region (residues 1-160) of SipB (SipB160) for secretion from bacterial cells. Attenuated S. typhimurium expressing recombinant IFN-γ (S. typhimurium (IFN-γ)) invaded the melanoma cells and induced cytotoxicity. Subcutaneous administration of S. typhimurium (IFN-γ) also efficiently inhibited tumour growth and prolonged the survival of C57BL/6 mice bearing B16F10 melanoma compared with administration of phosphate-buffered saline (PBS), unmodified S. typhimurium or S. typhimurium expressing empty vector (S. typhimurium [Vec]) in a natural killer (NK) cell-dependent manner. Moreover, genetically modified Salmonella, including S. typhimurium (IFN-γ), showed little toxicity to normal tissues with no observable adverse effects. However, S. typhimurium (IFN-γ)-mediated tumour suppression was attributed to direct killing of tumour cells rather than to stable anti-tumour immunity. Collectively, these results suggest that tumour-targeted therapy using S. typhimurium (IFN-γ) has potential for melanoma treatment.

Chromosome 11q13 deletion syndrome.

Chromosome 11q13 deletion syndrome has been previously reported as either otodental syndrome or oculo-oto-dental syndrome. The otodental syndrome is characterized by dental abnormalities and high-frequency sensorineural hearing loss, and by ocular coloboma in some cases. The underlying genetic defect causing otodental syndrome is a hemizygous microdeletion involving the FGF3 gene on chromosome 11q13.3. Recently, a new form of severe deafness, microtia (small ear) and small teeth, without the appearance of eye abnormalities, was also reported. In this report, we describe a 1-year-old girl presenting with ptosis of the left upper eyelid, right auricular deformity, high-arched palate, delayed dentition, simian line on the right hand, microcephaly, and developmental delay. In this patient, we identified a deletion in the chromosome 11q13.2-q13.3 (2.75 Mb) region by using an array-comparative genomic hybridization analysis. The deletion in chromosome 11q13 results in a syndrome characterized by variable clinical manifestations. Some of these manifestations involve craniofacial dysmorphology and require a functional workup for hearing, ophthalmic examinations, and long-term dental care.

Ictal sinus pause and myoclonic seizure in a child.

Ictal tachycardia and bradycardia are common arrhythmias; however, ictal sinus pause and asystole are rare. Ictal arrhythmia is mostly reported in adults with temporal lobe epilepsy. Recently, ictal arrhythmia was recognized as a major warning sign of sudden unexpected death in epilepsy. We present an interesting case of a child with ictal sinus pause and asystole. A 27-month-old girl was hospitalized due to 5 episodes of convulsions during the past 2 days. Results of routine electroencephalography (EEG) were normal, but she experienced brief generalized tonic seizure for 3 days. During video-monitored EEG and echocardiography (ECG), she showed multiple myoclonic seizures simultaneously or independently, as well as frequent sinus pauses. After treatment with valproic acid, myoclonus and generalized tonic seizures were well controlled and only 2 sinus pauses were seen on 24-hour Holter ECG monitoring. Sinus dysfunction should be recognized on EEG, and it can sometimes be treated successfully with only antiepileptic medication.

Norovirus in benign convulsions with mild gastroenteritis.

BACKGROUND: Benign convulsions with gastroenteritis (CwG) are defined as afebrile convulsions accompanying symptoms of gastroenteritis without evidence of laboratory derangement. Although the main pathogen has been known as rotavirus, since the introduction of rotavirus vaccine, associated viruses with CwG may have changed. Thus, we evaluated the viral association of CwG for patients admitting for recent 2.5 years. METHODS: All patients hospitalized for CwG between November 2012 and May 2015 were included in our study. Stool specimens were tested with reverse transcription polymerase chain reaction for detecting norovirus and astrovirus and with enzyme immunoassay for rotavirus and enteric adenovirus. Clinical data was gathered via chart review. RESULTS: Fifty patients were included. Except four patients who failed to collect stool samples, 46 patients were tested. Causative diarrheal viruses were detected in 38 patients and they were 29 norovirus, four rotavirus, four adenovirus, and one astrovirus. Norovirus was commonly identified during the months of November and December. No difference of the clinical characteristics and laboratory value was noted according to the number of seizure episodes. CONCLUSIONS: Norovirus is a common pathogen in CwG. Understanding the viral associations can facilitate recognition of CwG.

Epilepsy in children with a history of febrile seizures.

PURPOSE: Febrile seizure, the most common type of pediatric convulsive disorder, is a benign seizure syndrome distinct from epilepsy. However, as epilepsy is also common during childhood, we aimed to identify the prognostic factors that can predict epilepsy in children with febrile seizures. METHODS: The study comprised 249 children at the Korea University Ansan Hospital who presented with febrile seizures. The relationship between the subsequent occurrence of epilepsy and clinical factors including seizure and fever-related variables were analyzed by multivariate analysis. RESULTS: Twenty-five patients (10.0%) had additional afebrile seizures later and were diagnosed with epilepsy. The subsequent occurrence of epilepsy in patients with a history of febrile seizures was associated with a seizure frequency of more than 10 times during the first 2 years after seizure onset (P<0.001). Factors that were associated with subsequent occurrence of epilepsy were developmental delay (P<0.001), preterm birth (P=0.001), multiple seizures during a febrile seizure attack (P=0.005), and epileptiform discharges on electroencephalography (EEG) (P=0.008). Other factors such as the age at onset of first seizure, seizure duration, and family history of epilepsy were not associated with subsequent occurrence of epilepsy in this study. CONCLUSION: Febrile seizures are common and mostly benign. However, careful observation is needed, particularly for prediction of subsequent epileptic episodes in patients with frequent febrile seizures with known risk factors, such as developmental delay, history of preterm birth, several attacks during a febrile episode, and epileptiform discharges on EEG.

Therapeutic Outcomes and Prognostic Factors in Childhood Absence Epilepsy.

BACKGROUND AND PURPOSE: Childhood absence epilepsy (CAE) is one of the most common types of pediatric epilepsy. It is generally treated with ethosuximide (ESM), valproic acid (VPA), or lamotrigine (LTG), but the efficacy and adverse effects of these drugs remain controversial. This study compared initial therapy treatment outcomes, including VPA-LTG combination, and assessed clinical factors that may predict treatment response and prognosis. METHODS: Sixty-seven patients with typical CAE were retrospectively enrolled at the Korea University Medical Center. We reviewed patients' clinical characteristics, including age of seizure onset, seizure-free interval, duration of seizure-free period, freedom from treatment failure, breakthrough seizures frequency, and electroencephalogram (EEG) findings. RESULTS: The age at seizure onset was 7.9±2.7 years (mean±SD), and follow-up duration was 4.4±3.7 years. Initially, 22 children were treated with ESM (32.8%), 23 with VPA (34.3%), 14 with LTG (20.9%), and 8 with VPA-LTG combination (11.9%). After 48 months of therapy, the rate of freedom from treatment failure was significantly higher for the VPA-LTG combination therapy than in the three monotherapy groups (p=0.012). The treatment dose administrated in the VPA-LTG combination group was less than that in the VPA and LTG monotherapy groups. The shorter interval to loss of 3-Hz spike-and-wave complexes and the presence of occipital intermittent rhythmic delta activity on EEG were significant factors predicting good treatment response. CONCLUSIONS: This study showed that low-dose VPA-LTG combination therapy has a good efficacy and fewer side effects than other treatments, and it should thus be considered as a firstline therapy in absence epilepsy.