Adolescent-Onset Epilepsy: Clinical Features and Predictive Factors for First-Year Seizure Freedom.

BACKGROUND: Teenagers with epilepsy require special attention to ensure a successful treatment journey. Our objective was to delineate the clinical characteristics of adolescent-onset epilepsy (AOE) and investigate the predictive factors influencing first-year seizure freedom. METHODS: We retrospectively analyzed the medical records of patients whose first seizure occurred between the ages of 10 and 19 years and who received antiseizure medication (ASM) treatment for at least 12 months. RESULTS: A total of 67 patients were included, with an average age of 13.5 ± 2.3 years at the onset of their first seizure. The average follow-up period was 45.2 ± 16.9 months, and comorbid conditions were present in 23 patients (34.3%). The majority of the patient population (83.6%) was affected by generalized epilepsy. The most common epilepsy syndrome was epilepsy with generalized tonic-clonic seizures alone at 70.1% (juvenile myoclonic epilepsy 11.9%, juvenile absence epilepsy 1.5%). Regarding ASM treatment, 31 patients (46.3%) received monotherapy, and 28 (41.8%) received dual therapy. Five patients (7.5%) encountered issues related to medication adherence. First-year seizure freedom was observed in 42 patients (62.7%). In multivariate analysis, a negative family history of epilepsy (odds ratio 12.1, 95% confidence interval 1.27-115.44, p = 0.030) was identified as a strong predictive factor of first-year seizure freedom, along with ASM monotherapy (odds ratio 3.99, 95% confidence interval 1.05-15.21, p = 0.043). CONCLUSION: These findings suggest that AOE typically exhibits effective control of seizures. A negative family history of epilepsy and ASM monotherapy emerges as robust predictor of achieving favorable outcomes within the early stage of treatment.

Psychiatric and behavioral concerns of perampanel with concomitant levetiracetam in children with epilepsy.

PURPOSE: Perampanel (PER) is expanding the therapeutic scope for pediatric epilepsy owing to its efficacy and favorable safety profile. However, concerns about psychiatric and behavioral adverse events (PBAEs) in combination therapy with levetiracetam (LEV) continue to contribute to hesitation in its prescription. We investigated the risk profiles for PBAEs when adding PER to pediatric epilepsy treatment and analyzed the differences according to the presence of concomitant LEV. METHODS: We retrospectively reviewed the medical records of children aged 4-18 years with epilepsy who were prescribed PER as adjunctive therapy from March 2016 to February 2023. We compared the occurrence and management of PBAEs between the PER without LEV and PER with LEV groups. The risk factors for PBAEs were also analyzed. RESULTS: Ninety-four patients (53 boys and 41 girls) were included in this study. The median age of total patients at the time of adding PER was 14.9 years (12.3-16.4 years), and 53 patients (56.4 %) had concomitant LEV. Forty-seven PBAEs occurred in 34 patients (36.2 %), with no significant differences depending on whether concomitant LEV is present or not. The most common PBAEs were aggression (14.9 %), irritability (9.6 %), affect lability (7.4 %), and acute psychosis (6.4 %). PBAEs occurred at a lower dosage (2-6 mg/day) in 70.6 % of the patients. In addition, 73.5 % of patients with PBAEs continued PER treatment by follow-up observation or by reducing the PER dosage. No risk factors, such as the presence of concomitant LEV or lamotrigine, any comorbid conditions, higher PER dosage (8-12 mg/day), two or more concomitant anti-seizure medications, and younger age (<13 years) at PER add-on, showed significant associations. CONCLUSION: When expanding the use of anti-seizure medications in pediatric patients, real-world evidence on safety issues is crucial for pediatric epileptologists. We confirmed that combination therapy with PER and LEV did not increase the risk profile of PBAEs.

Homeostatic regulation of neuronal excitability by probiotics in male germ-free mice.

Emerging evidence indicates that probiotics can influence the gut-brain axis to ameliorate somatic and behavioral symptoms associated with brain disorders. However, whether probiotics have effects on the electrophysiological activities of individual neurons in the brain has not been evaluated at a single-neuron resolution, and whether the neuronal effects of probiotics depend on the gut microbiome status have yet to be tested. Thus, we conducted whole-cell patch-clamp recording-assisted electrophysiological characterizations of the neuronal effects of probiotics in male germ-free (GF) mice with and without gut microbiome colonization. Two weeks of treatment with probiotics (Lactobacillus rhamnosus and Bifidobacterium animalis) significantly and selectively increased the intrinsic excitability of hippocampal CA1 pyramidal neurons, whereas reconstituting gut microbiota in GF mice reversed the effects of the probiotics leading to a decreased intrinsic excitability in hippocampal neurons. This bidirectional modulation of neuronal excitability by probiotics was observed in hippocampal neurons with corresponding basal membrane property and action potential waveform changes. However, unlike the hippocampus, the amygdala excitatory neurons did not show any electrophysiological changes to the probiotic treatment in either GF or conventionalized GF mice. Our findings demonstrate for the first time how probiotic treatment can have a significant influence on the electrophysiological properties of neurons, bidirectionally modulating their intrinsic excitability in a gut microbiota and brain area-specific manner.

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.

Clinical Profile and Predictors of Recurrent Simple Febrile Seizure.

BACKGROUND: Recurrent simple febrile seizure (SFS) refers to febrile seizure (FS) that recurs within 24 hours. Patients with recurrent SFS often undergo unnecessary neurodiagnostic tests. To address this, we compared the clinical characteristics of recurrent SFS with those of SFS and investigated the risk factors associated with recurrent SFS. METHODS: We retrospectively reviewed electronic medical records of patients aged six to 60 months who had been hospitalized for FS at two training hospitals between January 2016 and December 2019. The primary outcome was a comparison of the clinical features of patients with SFS and recurrent SFS. Additionally, the risk factors associated with seizure recurrence within 24 hours were evaluated. RESULTS: Three quarters (n = 191, 75.2%) of the 254 enrolled patients experienced a single seizure episode during the febrile illness period. The remaining 63 patients (24.8%) were diagnosed with recurrent SFS. Significant differences between SFS and recurrent SFS were observed in the history of recurrent SFS, time from fever onset to seizure, and body temperature on hospital arrival. Multiple logistic regression analysis revealed that a history of previous recurrent SFS (odds ratio [OR] 10.161) and a body temperature below 39°C on arrival (OR 2.377) were significantly associated with early seizure recurrence. CONCLUSIONS: This study highlights that early FS recurrence is common and has a self-limiting clinical course similar to that of SFS. We recommend close monitoring of the patient for six to eight hours when a history of early recurrence is present or if the seizure occurs at a low body temperature.

Seizure Evolution and Outcome in Pediatric Autoimmune Encephalitis.

BACKGROUND: Our study aimed to characterize seizure incidence and seizure outcome of pediatric autoimmune encephalitis (AE) focusing on subgroup analysis based on antibody (Ab). METHODS: Among 110 pediatric patients with AE, we compared seizure characteristics and outcomes in 68 patients with seizure, who satisfied the proposed criteria of pediatric AE. Accordingly, patients were classified into three groups, anti-myelin oligodendrocyte glycoprotein (anti-MOG) AE, anti-N-methyl-D-aspartic acid receptor (anti-NMDAR) AE, and Ab-negative AE. Univariate and multivariate analyses were performed to evaluate the risk factors for postencephalitic seizures, defined as persisting seizures six months after onset. RESULTS: Seizure incidence in the anti-NMDAR (88.9%) and Ab-negative (71.1%) groups differed from anti-MOG group (37.8%). Median seizure frequency within six months was higher in the Ab-negative group (6.0, interquartile range [IQR] 3.0 to 13.0) than in the anti-NMDAR group (3.0, IQR 2.0 to 4.5) and anti-MOG group (2.0, IQR 1.0 to 5.0). Patients in the Ab-negative group tended to develop postencephalitic seizures more frequently and have a lower seizure freedom rate than those in the anti-NMDAR and anti-MOG groups. Ab-negative status, high seizure frequency within six months, and the presence of status epilepticus were associated with the development of postencephalitic seizures on univariate analysis. On multivariate analysis, Ab-negative status remained the only significant variable linked with postencephalitic seizure (odds ratio, 4.17; 95% confidence interval, 1.02 to 18.05). CONCLUSIONS: We delineated the seizure incidence, evolution, and outcome of pediatric patients with Ab-positive and Ab-negative AE. Ab-negative status is predictive of higher seizure burden, more frequent development of postencephalitic seizures, and less favorable seizure outcome than anti-NMDAR and anti-MOG Ab-positive status.

Prospective Associations between Cumulative Average Intake of Flavonoids and Hypertension Risk in the CArdioVascular Disease Association Study (CAVAS).

In this study, we aimed to investigate the prospective associations and their shapes between the dietary intake of total flavonoids and their seven subclasses and hypertension risk in a prospective cohort, the KoGES_CArdioVascular disease Association Study (CAVAS), and to consider obesity status as an additional factor. A total of 10,325 adults aged 40 years and older were enrolled at baseline, and 2159 patients were newly diagnosed with hypertension during a median follow-up of 4.95 years. Cumulative dietary intake was estimated using a repeated food frequency questionnaire. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were estimated using modified Poisson models with a robust error estimator. We observed nonlinear inverse associations between total and seven subclasses of flavonoids and hypertension risk, although there was no significant association between total flavonoids and flavones with hypertension risk in the highest quartile. For men, these inverse associations tended to be pronounced in the high BMI group, particularly for anthocyanins and proanthocyanidins [IRR (95% CI) in overweight/obese men: 0.53 (0.42-0.67) for anthocyanins; 0.55 (0.42-0.71) for proanthocyanidins]. Our results suggested that consumption of dietary flavonoids may not be dose-responsive but is inversely associated with hypertension risk, particularly among overweight/obese men.

Short-term clinical outcomes of onasemnogene abeparvovec treatment for spinal muscular atrophy.

INTRODUCTION: Spinal muscular atrophy (SMA) is a degenerative neuromuscular disorder long recognized as the most common genetic cause of infantile mortality described so far. However, the emergence of some innovative therapies, such as nusinersen and onasemnogene abeparvovec (AVXS-101), have made it possible to change the disease course of SMA. METHODS: In this study, five SMA type 1 and one SMA type 2 patients who received AVXS-101 were enrolled (7-24 months of age when administered). They were all previously treated with nusinersen, 4-5 times including loading doses, but stopped nusinersen maintenance after injection of AVXS-101. Patients were regularly followed up with laboratory tests and functional assessments after administration. RESULTS: Liver enzymes (aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase) and monocyte count tended to be elevated but normalized after several weeks. Platelets and white blood cells were transiently decreased for a few weeks after injection. Prolonged elevation of liver enzymes was associated with steroid tapering earlier than 1 month post treatment. During the follow-up period (ranging from 5 to 17 months after injection), all patients showed improved motor function and there was no case of mortality or requirement for permanent ventilatory support. For one patient, use of bilevel positive airway pressure could be reduced from 16 h to 8 h a day during sleep at 6 months post treatment. CONCLUSION: Our experience of AVXS-101 treatment has shown that a single intravenous dose could be safe and effective for SMA patients without the need for any maintenance treatment.

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.

Effects of Combined Anti-Hypertensive and Statin Treatment on Memory, Fear Extinction, Adult Neurogenesis, and Angiogenesis in Adult and Middle-Aged Mice.

Hyperlipidemia and hypertension are modifiable risk factors for cognitive decline. About 25% of adults over age 65 use both antihypertensives (AHTs) and statins to treat these conditions. Recent research in humans suggests that their combined use may delay or prevent dementia onset. However, it is not clear whether and how combination treatment may benefit brain function. To begin to address this question, we examined effects of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and Captopril, an angiotensin-converting enzyme inhibitor (ACEI), administration on memory function, anxiety-like behavior, adult hippocampal neurogenesis and angiogenesis in adult and middle-aged male C57Bl/6J mice. In adult mice (3-months-old) combination (combo) treatment, as well as administration of each compound individually, for six weeks, accelerated memory extinction in contextual fear conditioning. However, pattern separation in the touchscreen-based location discrimination test, a behavior linked to adult hippocampal neurogenesis, was unchanged. In addition, dentate gyrus (DG) neurogenesis and vascularization were unaffected. In middle-aged mice (10-months-old) combo treatment had no effect on spatial memory in the Morris water maze, but did reduce anxiety in the open field test. A potential underlying mechanism may be the modest increase in new hippocampal neurons (~20%) in the combo as compared to the control group. DG vascularization was not altered. Overall, our findings suggest that statin and anti-hypertensive treatment may serve as a potential pharmacotherapeutic approach for anxiety, in particular for post-traumatic stress disorder (PTSD) patients who have impairments in extinction of aversive memories.