Epidemiology and Healthcare Utilization in Pediatric Multiple Sclerosis and Neuromyelitis Optica: A Nationwide Population-Based Study in South Korea (2016-2020).

Pediatric multiple sclerosis (MS) and neuromyelitis optica (NMO) are rare acquired demyelinating syndrome with limited epidemiological data available, particularly in non-Western setting. This study aimed to demonstrate the epidemiology of pediatric MS and NMO in South Korea and to analyze of healthcare utilization and economic burden associated with these conditions. Using a nationwide population-based database from the Korean Health Insurance Review and Assessment Service database, we identified pediatric cases (age < 20 years) of MS and NMO from 2016 to 2020. We analyzed incidence, prevalence, healthcare utilization and medical costs. The study found low age-standardized incidence and prevalence rates for pediatric MS and NMO in South Korea. There was a marked disparity in healthcare utilization between urban and rural areas. Most healthcare interactions occurred in tertiary hospitals in urban settings, particularly in Seoul. The study also highlighted the substantial economic burden associated with the management of rare diseases, with annual variability in medical costs. Pediatric MS and NMO are extremely rare in South Korea, with significant regional disparity in healthcare utilization. The findings emphasize the need for targeted healthcare policies to improve access and reduce disparities, particularly for chronic and rare diseases requiring specialized care.

A Case of Chromosome 17q12 Deletion Syndrome with Type 2 Mayer-Rokitansky-Küster-Hauser Syndrome and Maturity-Onset Diabetes of the Young Type 5.

Chromosome 17q12 deletion syndrome (OMIM #614527) is a rare genetic disorder associated with a heterozygous 1.4-1.5 Mb deletion at chromosome 17q12, leading to a spectrum of clinical manifestations, including kidney abnormalities, neurodevelopmental delay, maturity-onset diabetes of the young type 5 (MODY5), and Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. We present the case of a 14-year-old Korean female diagnosed with chromosome 17q12 deletion syndrome, confirmed by chromosomal microarray analysis. The patient exhibited MODY5 with pancreatic agenesis, MRKH syndrome, dysmorphic facial features, developmental delay, kidney rotation anomaly, portal vein thrombosis with liver hypoplasia, short stature, and scoliosis. Management involved the initiation of multiple daily insulin injections for diabetes control, gynecological evaluation for MRKH syndrome, and multidisciplinary care for associated complications. This case highlights the complexity and varied organ involvement in chromosome 17q12 deletion syndrome. A comprehensive and multidisciplinary approach is crucial for the management of affected individuals, including regular monitoring, tailored interventions across various medical specialties, and providing psychosocial support.

Sex Differences in the Preventive Effect of Cardiovascular and Metabolic Therapeutics on Dementia.

Dementia is a clinical syndrome characterized by progressive impairment of cognitive and functional abilities. As currently applied treatments for dementia can only delay the progression of dementia and cannot fundamentally cure it, much attention is being paid to reducing its incidence by preventing the associated risk factors. Cardiovascular and metabolic diseases are well-known risk factors for dementia, and many studies have attempted to prevent dementia by treating these risk factors. Growing evidence suggests that sex-based factors may play an important role in the pathogenesis of dementia. Therefore, a deeper understanding of the differences in the effects of drugs based on sex may help improve their effectiveness. In this study, we reviewed sex differences in the impact of therapeutics targeting risk factors for dementia, such as cardiovascular and metabolic diseases, to prevent the incidence and/or progression of dementia.

Incidence of Pediatric Acute Disseminated Encephalomyelitis During the Coronavirus Disease 2019 Pandemic in South Korea.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating disorder of the central nervous system that is usually triggered by infections. We aimed to determine the temporal trends in the incidence of ADEM before and during the pandemic and their correlation with viral epidemiology. METHODS: We conducted a nationwide, population-based, retrospective, ADEM cohort study by using the Health Insurance Review and Assessment Service database. New-onset ADEM was defined as a patient (age <19 years) who was hospitalized with a diagnostic code of G04.0, G36.8, and G36.9 and a prescription of intravenous methylprednisolone. The National Infectious Disease Surveillance System was used to collect the nationwide viral epidemics. RESULTS: A total of 185 new-onset pediatric ADEM cases were included. The mean patient age was 7.0 ± 4.9 years. The incidence of ADEM was 0.34 to 0.48 of 100,000 persons per year before the pandemic, which dropped to 0.22 of 100,000 persons per year during the first pandemic year. The risk of ADEM occurrence was approximately 1.74% higher during the prepandemic years compared with the first pandemic year (odds ratio = 1.017, P = 0.009). There was a weak positive correlation between acute respiratory viral infection and ADEM incidence (r = 0.28, P = 0.03). CONCLUSION: This study demonstrates how infection control during the early coronavirus disease 2019 (COVID-19) pandemic influenced the incidence of ADEM. The low incidence of ADEM in the early COVID-19 pandemic may be related to the decline in acute respiratory viral infections, which are potential triggers of ADEM.

Corrigendum: Incidence of Guillain-Barré syndrome in South Korea during the early COVID-19 pandemic.

[This corrects the article DOI: 10.3389/fneur.2023.1125455.].

Incidence of Guillain-Barré syndrome in South Korea during the early COVID-19 pandemic.

Objectives: Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy, often triggered by infection. We aimed to investigate how the incidence of GBS changed in the early stages of the coronavirus 2019 (COVID-19) pandemic when nationwide infections declined due to non-pharmaceutical interventions. Methods: We conducted a nationwide population-based retrospective GBS cohort study using data from the Health Insurance Review and Assessment Service of Korea. Patients with new-onset GBS were defined as those who were first hospitalized between 1 January 2016 and 31 December 2020 with an International Classification of Disease, 10th Revision code, for GBS (G61.0) as a primary diagnosis. The incidence of GBS in the pre-pandemic years (2016-2019) was compared with that in the first pandemic year (2020). Nationwide epidemiological data for infections were collected from the national infectious disease surveillance system. A correlation analysis was performed to determine the incidence of GBS and nationwide trends of various infections. Results: Overall, 3,637 new-onset GBS cases were identified. The age-standardized incidence of GBS in the first pandemic year was 1.10 (95% confidence interval, 1.01-1.19) per 100,000 persons. Compared to the first pandemic year, the incidence of GBS during the pre-pandemic years (1.33-1.68/100,000 persons/year) was significantly higher, with incidence rate ratios of 1.21-1.53 (P < 0.001). Nationwide cases of upper respiratory viral infections were significantly reduced in the first pandemic year; however, Campylobacter infections peaked in the summer of the pandemic. The nationwide epidemiology of parainfluenza virus, enterovirus, and Campylobacter infections correlated positively with GBS incidence. Conclusion: The overall GBS incidence decreased in the early stages of the COVID-19 pandemic, which can be attributed to the dramatic reduction in viral illnesses due to public measures.

The Korean undiagnosed diseases program phase I: expansion of the nationwide network and the development of long-term infrastructure.

BACKGROUND: Phase I of the Korean Undiagnosed Diseases Program (KUDP), performed for 3 years, has been completed. The Phase I program aimed to solve the problem of undiagnosed patients throughout the country and develop infrastructure, including a data management system and functional core laboratory, for long-term translational research. Herein, we share the clinical experiences of the Phase I program and introduce the activities of the functional core laboratory and data management system. RESULTS: During the program (2018-2020), 458 patients were enrolled and classified into 3 groups according to the following criteria: (I) those with a specific clinical assessment which can be verified by direct testing (32 patients); (II) those with a disease group with genetic and phenotypic heterogeneity (353 patients); and (III) those with atypical presentations or diseases unknown to date (73 patients). All patients underwent individualized diagnostic processes based on the decision of an expert consortium. Confirmative diagnoses were obtained for 242 patients (52.8%). The diagnostic yield was different for each group: 81.3% for Group I, 53.3% for Group II, and 38.4% for Group III. Diagnoses were made by next-generation sequencing for 204 patients (84.3%) and other genetic testing for 35 patients (14.5%). Three patients (1.2%) were diagnosed with nongenetic disorders. The KUDP functional core laboratory, with a group of experts, organized a streamlined research pipeline covering various resources, including animal models, stem cells, structural modeling and metabolic and biochemical approaches. Regular data review was performed to screen for candidate genes among undiagnosed patients, and six different genes were identified for functional research. We also developed a web-based database system that supports clinical cohort management and provides a matchmaker exchange protocol based on a matchbox, likely to reinforce the nationwide clinical network and further international collaboration. CONCLUSIONS: The KUDP evaluated the unmet needs of undiagnosed patients and established infrastructure for a data-sharing system and future functional research. The advancement of the KUDP may lead to sustainable bench-to-bedside research in Korea and contribute to ongoing international collaboration.

Mortality, Disability, and Prognostic Factors of Status Epilepticus: A Nationwide Population-Based Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: The outcome of status epilepticus (SE) largely varies depending on clinical characteristics. Risk stratification is necessary for tailoring the aggressiveness of treatment and predicting outcomes of individual patients with SE. In this study, we assessed differences in mortality, neurologic disability, and prognostic factors associated with SE across sociodemographic and clinical characteristics. METHODS: We conducted a nationwide population-based retrospective cohort study using the National Health Insurance Service (NHIS) database linked with the national death and disability registries. SE was identified from admission or emergency department visits using a diagnostic code of G41 from the International Classification of Diseases, 10th Revision. Individuals with new-onset SE that occurred from January 1, 2010, to December 31, 2018, were included. Active epilepsy, refractoriness of SE, potential etiology, and comorbidities were ascertained by diagnostic codes and/or prescription records from the NHIS database as potential prognostic factors. Outcomes included 30-day and 1-year mortality and neurologic disabilities after SE. Prognostic factors for mortality were assessed by the Cox regression hazard model. We performed a subgroup analysis according to age: pediatric SE (age <20 years) and adult SE (age ≥20 years). RESULTS: A total of 33,814 patients with new-onset SE were included (6,818 children/adolescents and 26,996 adults). The 30-day mortality was 8.5% (1.8% in pediatric SE and 10.2% in adult SE), and the 1-year mortality was 25.1% (4.6% in pediatric SE and 30.3% in adult SE). Overall, 10.7% of patients newly acquired neurologic disabilities after SE, with the highest incidence in children aged 5-9 years (21.3%). Intractable epilepsy developed in 0.8% of entire SE. Old age, presence of acute etiology, and refractoriness were poor prognostic factors for mortality in both pediatric and adult SE. Male sex, low economic status, no active epilepsy, and comorbidities were additional factors for a poor prognosis in adults. DISCUSSION: New-onset SE was associated with substantial mortality and disability. Although SE-related mortality was higher in adults, disabilities developed more commonly in children and adolescents. The major determinants of mortality differed between pediatric and adult SE.

Expanding the clinical phenotype and genetic spectrum of PURA-related neurodevelopmental disorders.

BACKGROUND: PURA-related neurodevelopmental disorders (PURA-NDDs) include 5q31.3 deletion syndrome and PURA syndrome. PURA-NDDs are characterized by neonatal hypotonia, moderate to severe global developmental delay/intellectual disability (GDD/ID), facial dysmorphism, epileptic seizures, nonepileptic movement disorders, and ophthalmological problems. PURA-NDDs have recently been identified and underestimated in neurodevelopmental cohorts, but their diagnosis is still challenging. METHODS: We retrospectively reviewed the clinical characteristics, genetic spectrum, and diagnostic journey of patients with PURA-NDDs. RESULTS: We report 2 patients with 5q31.3 microdeletion and 5 with PURA pathogenic variants. They demonstrated hypotonia (7/7, 100%), feeding difficulties (4/5, 80%), and respiratory problems (4/7, 57%) in the neonatal period. All of them had severe GDD/ID and could not achieve independent walking and verbal responses. Distinctive facial features of open-tented upper vermilion, long philtrum, and anteverted nares and poor visual fixation and tracking with or without nystagmus were most commonly found (5/7, 71.4%). There were no significant differences in clinical phenotypes between 5q31.3 microdeletion syndrome and PURA syndrome. PURA-NDDs need to be considered as a differential diagnosis in individuals who show severe hypotonia, including feeding difficulties since birth and severe developmental retardation with distinctive facial and ophthalmological features. CONCLUSIONS: Our data expands the phenotypic and genetic spectrum of PURA-NDD. Next-generation sequencing methods based on the detailed phenotypic evaluation would shorten the diagnostic delay and would help this rare disorder become a recognizable cause of neurodevelopmental delay.

Impact of mobile health application on data collection and self-management of epilepsy.

Recent advances in mobile health have enabled health data collection, which includes seizure and medication tracking and epilepsy self-management. We developed a mobile epilepsy management application, integrated with a hospital electronic health record (EHR). In this prospective clinical trial, we assessed whether the mobile application provides quality healthcare data compared to conventional clinic visits, and enhances epilepsy self-management for patients with epilepsy. The study population includes patients with epilepsy (ages 15 years and older) and caregivers for children with epilepsy. Participants were provided access to the application for 90 days. We compared healthcare data collected from the mobile application with data obtained from clinic visits. The healthcare data included seizure records, seizure triggering factors, medication adherence rate, profiles of adverse events resulting from anti-seizure medication (ASM), and comorbidity screenings. In addition, we conducted baseline and follow-up questionnaires after the 90-day period to evaluate how this mobile application improved epilepsy knowledge and self-efficacy in seizure management. Data of 99 participants (18 patients with epilepsy and 81 caregivers) were analyzed. Among 24 individuals who had seizures, we obtained detailed seizure records from 13 individuals through clinic visits and for 18 from the application. Aside from the 6 individuals who reported their medication adherence during clinic visitation, half of the study participants had adherence rates of over 70%, as monitored through the application. However, the adherence rates were not reliable due to high variability. Twenty-three individuals reported 59 adverse reactions on the application, whereas 21 individuals reported 24 adverse reactions during clinic visits. We collected comorbidity data from 4 individuals during clinic visits. In comparison, 64 participants underwent comorbidity self-screening on the application, and 2 of them were referred to neuropsychiatric services. Compared to rare/non-users, app users demonstrated significant improvement in epilepsy knowledge score (p < 0.001) and self-efficacy score (p = 0.038). In conclusion, mobile health technology would help patients and caregivers to record their healthcare data and aid in self-management. Mobile health technology would provide an influential clinical validity in epilepsy care when users engage and actively maintain records on the application.

Early-onset autosomal dominant GTP-cyclohydrolase I deficiency: Diagnostic delay and residual motor signs.

OBJECTIVE: Autosomal dominant (AD) guanosine triphosphate cyclohydrolase 1 (GCH1) deficiency is the most common cause of dopa-responsive dystonia (DRD). Patients with GCH1 deficiency are likely to experience diagnostic delay, but its consequences have not been described thoroughly in patients with early-onset disease. We describe the diagnostic delay and residual motor signs (RMS) observed in patients with early-onset (before 15 years of age) disease. METHODS: Twelve patients with early-onset AD GCH1 deficiency from a single center were included in the case series analysis. For the meta-analysis, the PubMed database was searched for articles on early-onset AD GCH1 deficiency published from 1995 to 2019. RESULTS: In the case series, the mean duration of diagnostic delay was 5.6 years. Two patients exhibited RMS, and four patients underwent orthopedic surgery. The literature search yielded 137 AD GCH1 deficiency cases for review; gait disturbance was reported in 92.7% of patients, diurnal fluctuation of symptoms in 91.9%, and RMS in 39%. The mean duration of diagnostic delay was 14.6 years overall: 12.0 years in RMS-negative patients and 21.2 years in RMS-positive patients. CONCLUSIONS: Diagnostic delay in early-onset AD GCH1 deficiency is more closely associated with later RMS. Early clinical suspicion, timely diagnosis, and levodopa treatment may reduce the occurrence of RMS in patients with early-onset AD GCH1 deficiency.

Deep Convolutional Neural Network Based Interictal-Preictal Electroencephalography Prediction: Application to Focal Cortical Dysplasia Type-II.

We aimed to differentiate between the interictal and preictal states in epilepsy patients with focal cortical dysplasia (FCD) type-II using deep learning-based classifiers based on intracranial electroencephalography (EEG). We also investigated the practical conditions for high interictal-preictal discriminability in terms of spatiotemporal EEG characteristics and data size efficiency. Intracranial EEG recordings of nine epilepsy patients with FCD type-II (four female, five male; mean age: 10.7 years) were analyzed. Seizure onset and channel ranking were annotated by two epileptologists. We performed three consecutive interictal-preictal classification steps by varying the preictal length, number of electrodes, and sampling frequency with convolutional neural networks (CNN) using 30 s time-frequency data matrices. Classification performances were evaluated based on accuracy, F1 score, precision, and recall with respect to the above-mentioned three parameters. We found that (1) a 5 min preictal length provided the best classification performance, showing a remarkable enhancement of >13% on average compared to that with the 120 min preictal length; (2) four electrodes provided considerably high classification performance with a decrease of only approximately 1% on average compared to that with all channels; and (3) there was minimal performance change when quadrupling the sampling frequency from 128 Hz. Patient-specific performance variations were noticeable with respect to the preictal length, and three patients showed above-average performance enhancements of >28%. However, performance enhancements were low with respect to both the number of electrodes and sampling frequencies, and some patients showed at most 1-2% performance change. CNN-based classifiers from intracranial EEG recordings using a small number of electrodes and efficient sampling frequency are feasible for predicting the interictal-preictal state transition preceding seizures in epilepsy patients with FCD type-II. Preictal lengths affect the predictability in a patient-specific manner; therefore, pre-examinations for optimal preictal length will be helpful in seizure prediction.

Clinical Spectrum of Myelin Oligodendrocyte Glycoprotein-Immunoglobulin G-Associated Disease in Korean Children.

BACKGROUND AND PURPOSE: The myelin oligodendrocyte glycoprotein (MOG) antibody is detected at a high rate in childhood acquired demyelinating syndrome (ADS). This study aimed to determine the diagnostic value of the MOG antibody in ADS and the spectrum of MOG-antibody-positive demyelinating diseases in children. METHODS: This study included 128 patients diagnosed with ADS (n=94) or unexplained encephalitis (n=34). The MOG antibody in serum was tested using an in-house live-cell-based immunofluorescence assay. RESULTS: The MOG antibody was detected in 48 patients (46 ADS patients and 2 encephalitis patients, comprising 23 males and 25 females). Acute disseminated encephalomyelitis (ADEM) (35.4%) was the most-common diagnosis, followed by the unclassified form (17.4%), isolated optic neuritis (ON) (15.2%), neuromyelitis optica spectrum disorder (13.0%), multiple sclerosis (MS) (10.8%), other clinically isolated syndromes [monophasic event except ADEM, isolated ON, or transverse myelitis (TM)] (8.7%), and unexplained encephalitis (4.3%). At the initial presentation, 35 out of the 46 patients with ADS had brain lesions detected in magnetic resonance imaging, and 54% of these 35 patients had encephalopathy. Nine of the 11 patients without brain lesions exhibited only ON. Thirty-nine percent of the patients experienced a multiphasic event during the mean follow-up period of 34.9 months (range 1.4-169.0 months). Encephalopathy at the initial presentation was frequently confirmed in the monophasic group (p=0.011). CONCLUSIONS: MOG antibodies were identified in all pediatric ADS phenotypes except for monophasic TM. Therefore, the MOG antibody test is recommended for all pediatric patients with ADS, especially before a diagnosis of MS and for patients without a clear diagnosis.

Characterization of Anti-seizure Medication Treatment Pathways in Pediatric Epilepsy Using the Electronic Health Record-Based Common Data Model.

The purpose of this pilot study was to analyze treatment pathways of pediatric epilepsy using the common data model (CDM) based on electronic health record (EHR) data. We also aimed to reveal whether CDM analysis was feasible and applicable to epilepsy research. We analyzed the treatment pathways of pediatric epilepsy patients from our institute who underwent antiseizure medication (ASM) treatment for at least 2 years, using the Observational Medical Outcomes Partnership (OMOP)-CDM. Subgroup analysis was performed for generalized or focal epilepsy, varying age of epilepsy onset, and specific epilepsy syndromes. Changes in annual prescription patterns were also analyzed to reveal the different trends. We also calculated the proportion of drug-resistant epilepsy by applying the definition of seizure persistence after application of two ASMs for a sufficient period of time (more than 6 months). We identified 1,192 patients who underwent treatment for more than 2 years (mean ± standard deviation: 6.5 ± 3.2 years). In our pediatric epilepsy cohort, we identified 313 different treatment pathways. Drug resistance, calculated as the application of more than three ASMs during the first 2 years of treatment, was 23.8%. Treatment pathways and ASM resistance differed between subgroups of generalized vs. focal epilepsy, different onset age of epilepsy, and specific epilepsy syndromes. The frequency of ASM prescription was similar between onset groups of different ages; however, phenobarbital was frequently used in children with epilepsy onset < 4 years. Ninety-one of 344 cases of generalized epilepsy and 187 of 835 cases of focal epilepsy were classified as medically intractable epilepsy. The percentage of drug resistance was markedly different depending on the specific electro-clinical epilepsy syndrome [79.0% for Lennox-Gastaut syndrome (LGS), 7.1% for childhood absence epilepsy (CAE), and 9.0% for benign epilepsy with centrotemporal spikes (BECTS)]. We could visualize the annual trend and changes of ASM prescription for pediatric epilepsy in our institute from 2004 to 2017. We revealed that CDM analysis was feasible and applicable for epilepsy research. The strengths and limitations of CDM analysis should be carefully considered when planning the analysis, result extraction, and interpretation of results.

Factors associated with stigma and depressive symptoms in family members of patients with epilepsy.

PURPOSE: Literature regarding family stigma related to epilepsy is scarce. This study investigated the prevalence of family stigma and depressive symptoms and the associated factors among the family members of patients with epilepsy. METHODS: In a cross-sectional study, Stigma Scale-Revised score ≥ 4 and Patient Health Questionnaire-9 score ≥ 10 were considered indicative of moderate-to-severe stigma and depressive symptoms, respectively. Stepwise logistic regression analyses were performed. RESULTS: Of the 482 family members, a mean age was 47.1 ±â€¯9.4 years, and 73.4% were female. Of the patients, a mean age was 25.5 ±â€¯16.7 years, and 45.0% were female. Idiopathic generalized epilepsy and focal epilepsy were noted in 22.4% and 65.6% of patients, respectively. Family stigma and depressive symptoms were noted in 10.0% and 11.2% of family members, respectively. Family stigma was significantly associated with high seizure frequency and being a sibling or offspring of a patient independent of their depressive symptoms. By contrast, depressive symptoms in family members were significantly associated with polytherapy, being parents of a patient, and neurological comorbidities independent of family stigma. In a subset of patients and their family, patients had higher proportion of stigma and depressive symptoms than their family. Depressive symptoms and stigma among patients were significantly correlated with those among parents, but not spouse. CONCLUSION: Family stigma is common in families with epilepsy and is closely related to depressive symptoms. Frequent seizures, polytherapy, neurological comorbidities, and the relationship to a patient may be factors that are independently associated with family stigma and depressive symptoms in family members.

Analysis of antiseizure drug-related adverse reactions from the electronic health record using the common data model.

OBJECTIVE: Antiseizure drugs (ASDs) are known to cause a wide range of adverse drug reactions (ADRs). Recently, electronic health care data using the common data model (CDM) have been introduced and commonly adopted in pharmacovigilance research. We aimed to analyze ASD-related ADRs using CDM and to assess the feasibility of CDM analysis in monitoring ADR in a single tertiary hospital. METHODS: We selected five ASDs: oxcarbazepine (OXC), lamotrigine (LTG), levetiracetam (LEV), valproic acid (VPA), and topiramate (TPM). Patients diagnosed with epilepsy and exposed to monotherapy with one of the ASDs before age 18 years were included. We measured four ADR outcomes: (1) hematologic abnormality, (2) hyponatremia, (3) elevation of liver enzymes, and (4) subclinical hypothyroidism. We performed a subgroup analysis to exclude the effects of concomitant medications. RESULTS: From the database, 1344 patients were included for the study. Of the 1344 patients, 436 were receiving OXC, 293 were receiving LTG, 275 were receiving LEV, 180 were receiving VPA, and 160 were receiving TPM. Thrombocytopenia developed in 14.1% of patients taking VPA. Hyponatremia occurred in 10.5% of patients taking OXC. Variable ranges of liver enzyme elevation were detected in 19.3% of patients taking VPA. Subclinical hypothyroidism occurred in approximately 21.5% to 28% of patients with ASD monotherapy, which did not significantly differ according to the type of ASD. In a subgroup analysis, we observed similar ADR tendencies, but with less thrombocytopenia in the TPM group. SIGNIFICANCE: The incidence and trends of ADRs that were evaluated by CDM were similar to the previous literature. CDM can be a useful tool for analyzing ASD-related ADRs in a multicenter study. The strengths and limitations of CDM should be carefully addressed.

Clinical and Genetic Spectrum of ATP1A3-Related Disorders in a Korean Pediatric Population.

BACKGROUND AND PURPOSE: The aim of this study was to expand the understanding of the genotype-phenotype spectrum of ATP1A3-related disorders and to evaluate the therapeutic effect of a ketogenic diet in patients with alternating hemiplegia of childhood (AHC). METHODS: The clinical information of 13 patients with ATP1A3 mutations was analyzed by performing retrospective chart reviews. Patients with the AHC phenotype who consented to ketogenic diet were included in the trial. RESULTS: Ten patients presented with the clinical phenotype of AHC, two patients presented with rapid-onset dystonia parkinsonism, and one patient presented with cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss. Two novel mutations of the AHC phenotype were identified: p.Ile363Thr and p.Asn743Ser. The clinical phenotypes of three mutations differed from those in previous reports: p.Arg597Pro, p.Thr769Pro, and p.Arg756Cys. One of the two patients who started a ketogenic diet experienced seizure provocation and so immediate stopped consuming the diet, while the other patient continued the ketogenic diet for 1 year, but this produced no clear benefit such as reduction of paroxysmal symptoms. CONCLUSIONS: Our study is the first case series of ATP1A3-related disorders to be described in Korea and which further expands the understanding of its genotype-phenotype spectrum. A ketogenic diet showed no clear benefit for the patients with AHC.

Change of centrotemporal spikes from onset to remission in self-limited epilepsy with centrotemporal spikes (SLECTS).

OBJECTIVE: To reveal the changes of centrotemporal spikes that occur during the disease course of self-limited epilepsy with centrotemporal spikes (SLECTS). METHOD: We retrospectively reviewed the serial EEGs of 63 patients with SLECTS from initial diagnosis to remission. There were 32 patients who did not undergo treatment and 31 patients who underwent treatment with oxcarbazepine (OXC). The change of occurrence or abundance, voltage, and location of centrotemporal spikes of serial EEGs were analyzed and compared between the two groups. Clinical seizure evidenced and reported was counted. The time gap between seizure remission and EEG remission was measured in the two groups. RESULT: Changes of occurrence or abundance of the centrotemporal spikes were either abrupt (sudden disappearance of the frequent spikes on following EEG) or gradual (decline in number over 2 or more serial EEGs). Pattern of spike disappearance was not significantly different between the medication naïve group and OXC treated group. The spike voltage or the location of centrotemporal spikes did not change during the disease course in most cases. Delay between seizure remission and EEG normalization was 3.34 ± 1.75 (mean ± standard deviation, range: 0.77-7.97) years in untreated patients and 3.03 ± 1.41 (0.95-6.61) years in OXC-treated group. CONCLUSION: Pattern of spike disappearance in SLECTS was either abrupt or gradual. Treatment with OXC had no effect in the disappearance pattern. Precise data regarding the pattern of disappearance and delay between seizure remission and EEG normalization can help to understand the evolution of spike in SLECTS and to predict the timing of normalization of EEG after seizure remission.

Does the new Korean term for epilepsy reduce the stigma for Korean adults with epilepsy?

PURPOSE: The purpose of this study was to evaluate differences in stigma, disclosure management of epilepsy, and knowledge about epilepsy between patients with epilepsy who recognized and did not recognize the new Korean term for epilepsy. METHODS: This was a cross-sectional, multicenter study. The Stigma Scale-Revised, the Disclosure Management Scale, the Patient Health Questionnaire-9, and a questionnaire assessing knowledge about epilepsy were used. The set of questionnaires had two versions, using either the old or new name for epilepsy. Multivariate logistic regression analyses were used. RESULTS: A total of 341 patients with epilepsy and 509 family members were recruited. Approximately 62% of patients felt some degree of epilepsy-related stigma. Mild stigma, severe concealment of epilepsy diagnosis, and increased knowledge about epilepsy were independently identified as factors associated with recognition of the new term in patients. Recognition of the new term was more prevalent in patients and family members with higher education, female family members, and family members having patients with younger age at seizure onset and shorter duration of epilepsy. There were no significant differences between the two types of questionnaires. About 81% of patients and 93% of family members had a positive attitude about renaming epilepsy. CONCLUSION: The use of the new Korean term for epilepsy (cerebroelectric disorder) increased knowledge about epilepsy but did not reduce stigma and concealment of epilepsy diagnosis in Korean adults with epilepsy. Higher education may be an important factor for knowing the new term in patients and family members.

Association Analysis of Interleukin-1ß, Interleukin-6, and HMGB1 Variants with Postictal Serum Cytokine Levels in Children with Febrile Seizure and Generalized Epilepsy with Febrile Seizure Plus.

BACKGROUND AND PURPOSE: Febrile seizure (FS) is a unique type of seizure that only occurs during childhood. Genelized epilepsy with febrile seizure plus (GEFS+) is a familial epilepsy syndrome associated with FS and afebrile seizure (AFS). Both seizure types are related to fever, but whether genetic susceptibility to inflammation is implicated in them is still unclear. To analyze the associations between postictal serum cytokine levels and genetic variants in the cytokine genes interleukin (IL)-1ß, IL-6, and high mobility group box-1 (HMGB1) in FS and GEFS+. METHODS: Genotyping was performed in 208 subjects (57 patients with FS, 43 patients with GEFS+, and 108 controls) with the SNaPshot assay for IL-1ß-31 (rs1143627), IL-1ß-511 (rs16944), IL-6-572 (rs1800796), and HMGB1 3814 (rs2249825). Serum IL-1ß, IL-6, and HMGB1 levels were analyzed within 2 hours after seizure attacks using the ELISA in only 68 patients (38 FS, 10 GEFS+, and 20 controls). The allele distribution, genotype distribution, and correlations with serum cytokine levels were analyzed. RESULTS: Near-complete linkage disequilibrium exists between IL-1ß-31 and IL-1ß-511 variants. CT genotypes of these variants were associated with significantly higher postictal serum IL-1ß levels than were CC+TT genotypes in FS (both p<0.05). CT genotypes of IL-1ß-31 and IL-1ß-511 variants were more strongly associated with FS than were CC+TT genotypes (odds ratio=1.691 and 1.731, respectively). For GEFS+, serum IL-1ß levels after AFS for CT genotypes of IL-1ß-31 and IL-1ß-511 were also higher than for CC+TT genotypes. No significant associations were found for IL-6 and HMGB1. CONCLUSIONS: Genetic variants located in IL-1ß-31 and IL-1ß-511 promotor regions are correlated with higher postictal IL-1ß levels in FS. These results suggest that IL-1 gene cluster variants in IL-1ß-31 and IL-1ß-511 are a host genetic factor for provoking FS in Korean children.