Feasibility of mobile phone application "Epilepsy care" for self-management of children and adolescents with epilepsy in Phramongkutklao hospital: A randomized controlled trial.

Epilepsy is a common neurological disorder in children. Mobile applications have shown potential in improving self-management for patients with chronic illnesses. To address language barriers, we developed the first Thai version of the "Epilepsy care" mobile application for children and adolescents with epilepsy in Thailand. A prospective, randomized controlled trial with 220 children and adolescents living with epilepsy who had a smartphone and were treated at the pediatric neurology clinic was conducted, with one group using the mobile application and the other receiving standard epilepsy guidance. The primary outcome assessed epilepsy self-management using the Pediatric Epilepsy Self-Management Questionnaire (PEMSQ) in the Thai version, which comprised 27 questions. These questions aimed to determine knowledge, adherence to medications, beliefs about medication efficacy, and barriers to medication adherence. The secondary outcome evaluated seizure frequency at baseline, 3, and 6 months after initiation of an application. Eighty-five participants who were randomized to a mobile application achieved significantly higher PEMSQ scores in the domain of barriers to medication adherence (p < 0.05) at 6 months follow-up. Other domains of PEMSQ showed no statistically significant difference. Baseline median seizure frequencies per month were 7 in the control group and 5.5 in the intervention group. At 3 and 6 months, these decreased significantly to 1.5 and 1 for the control group and 2.5 and 1 for the intervention group (p < 0.001). In addition, the study revealed that 94.9 % of the participants in a mobile application group were highly satisfied with using application. These findings suggest that the mobile application "Epilepsy care" may serve as an effective adjunctive therapy to enhance self-management and seizure control in children and adolescents with epilepsy.

Mitochondrial genome diversity of Balamuthia mandrillaris revealed by a fatal case of granulomatous amoebic encephalitis.

Introduction: Balamuthia (B.) mandrillaris is a free-living amoeba that can cause rare yet fatal granulomatous amoebic encephalitis (GAE). However, efficacious treatment for GAE is currently unavailable, especially when genomic studies on B. mandrillaris are limited. Methods: In this study, B. mandrillaris strain KM-20 was isolated from the brain tissue of a GAE patient, and its mitochondrial genome was de novo assembled using high-coverage Nanopore long reads and Illumina short reads. Results and Discussion: Phylogenetic and comparative analyses revealed a range of diversification in the mitochondrial genome of KM-20 and nine other B. mandrillaris strains. According to the mitochondrial genome alignment, one of the most variable regions was observed in the ribosomal protein S3 (rps3), which was caused by an array of novel protein tandem repeats. The repeating units in the rps3 protein tandem region present significant copy number variations (CNVs) among B. mandrillaris strains and suggest KM-20 as the most divergent strain for its highly variable sequence and highest copy number in rps3. Moreover, mitochondrial heteroplasmy was observed in strain V039, and two genotypes of rps3 are caused by the CNVs in the tandem repeats. Taken together, the copy number and sequence variations of the protein tandem repeats enable rps3 to be a perfect target for clinical genotyping assay for B. mandrillaris. The mitochondrial genome diversity of B. mandrillaris paves the way to investigate the phylogeny and diversification of pathogenic amoebae.

Clinical Outcomes and Diagnostic Consistency of Serum and CSF Tumor Markers in Pediatric Intracranial Germ Cell Tumors in Thailand: A Multicenter Study.

The diagnostic and treatment outcomes of intracranial germ cell tumors (ICGCTs) among low and middle income countries are limited. A total of 63 ICGCTs patients with a median age of 11.6 years were studied. A 30 (47.6%) and 33 (52.4%) patients were classified as pure germinomas and nongerminomatous germ cell tumors (NGGCTs), respectively. The concordances between serum and cerebrospinal fluid (CSF) alpha-fetoprotein (84.3%) and beta-human chorionic gonadotropin (68.4%) were addressed. The 5-year overall survival (OS) and event-free survival (EFS) rates of pure germinomas versus NGGCTs were 83.9 versus 69.1% and 74.6 versus 57.7%, respectively. Patients undergoing radiation had higher 5-year OS and EFS than those without radiation treatment with P < .001. Chemotherapy combined with radiation is a cornerstone treatment to achieve outcomes. Adverse prognostic factors included age <8 years, surgery, and nonradiation treatment. Either serum or CSF tumor markers were adequately required as a diagnostic test among patients with ICGCTs.

Standard and high dose ergocalciferol regimens for treatment of hypovitaminosis D in epileptic children and adolescents.

OBJECTIVES: Children with epilepsy are at increased risk of vitamin D deficiency. We aimed to compare the effect of two ergocalciferol regimens given for 90 days. METHODS: Epileptic patients aged 5-18 years who received at least one antiepileptic drug (AED) for more than 6 months and had serum 25-OHD <30 ng/mL were randomized to receive 20,000 IU/10 d (standard dose, n=41) or 60,000 IU/10 d (high dose, n=41) of oral ergocalciferol. Serum Ca, P, Mg, ALP, iPTH and urine Ca/Cr ratio were measured at baseline and after 90 days of treatment. Change in serum 25-OHD and vitamin D status after treatment was evaluated. RESULTS: The initial serum 25-OHD in the standard dose and high dose group was 19.5 ± 4.9 and 18.4 ± 4.6 ng/mL, respectively. Serum 25-OHD after treatment was significantly higher in the high dose group (39.0 ± 11.5 vs. 27.5 ± 8.6 ng/mL, p<0.05). The average increase in serum 25-OHD in the high dose and standard dose group was 20.6 ± 11.4 and 7.2 ± 7.5 ng/mL, respectively (p<0.05). Normalized serum 25-OHD was achieved in 80.5% of the high dose group compared to 36.6% of the standard dose group (p<0.05). No adverse events were found. Patients with a BMI Z-score>0 had a 2.5 times greater risk of continued hypovitaminosis D after treatment compared to those with a BMI Z-score<0 (95% CI: 1.0-5.9, p<0.05). CONCLUSIONS: Oral ergocalciferol 60,000 IU/10 d for 90 days was more effective at normalizing serum 25-OHD than 20,000 IU/10 d in epileptic children and adolescents who were receiving AEDs.

Survey of local cannabidiol use in parents of children with epilepsy in Thailand: the prevalence, perceptions, and knowledge.

BACKGROUND: In 2019, Thailand legalized cannabidiol (CBD) for intractable epilepsy. The purpose of this study was to collect information regarding the experience and knowledge of CBD use in pediatric epilepsy. To the best of our knowledge, this is the first CBD survey in pediatric epilepsy in Southeast Asia. METHOD: We performed a cross-sectional survey among all parents of pediatric epilepsy patients seen in the Pediatric Neurology Clinic at Phramongkutklao Hospital, Bangkok, Thailand between November 2018 and July 2020. The survey comprised 34 questions that assessed the demographics, knowledge, experiences, and opinions of parents/guardians regarding CBD use. The results were summarized using descriptive statistics. In addition, logistic regression was used to predict the factors for CBD use. RESULTS: Overall, 166 respondents (100%) participated in the study. Among the respondents, 9% have experienced using CBD; 56.25% of these reported reduced seizure frequency. CBD products were mostly obtained from folk healers (31.25%) and foreign products (25%). Common adverse effects included headache and nausea (31.5%). The number of anti-seizure medications (OR: 12.28, 95% CI: 1.27-118.8), knowledge of CBD as treatment for epilepsy (OR: 14.7, 95% CI: 1.43-150.87), and knowledge of CBD side effects (OR: 12.73, 95% CI: 2.77-58.43) were factors significantly associated with CBD use. Regarding CBD knowledge, our survey showed 80.72% of the respondents did not know the CBD compound for treating epilepsy, and 89.16% were not aware of CBD side effects. Interestingly, despite a lack of knowledge, 77.11% of the respondents expressed willingness to participate in future CBD trials. CONCLUSION: Our survey highlights that half of the parents of patients who previously used CBD reported reduced seizure frequency; however, none became seizure-free. Additionally, there were gaps in knowledge regarding the use of CBD. These findings suggest that the implementation of cannabidiol knowledge is crucial for both public and healthcare professionals. Survey limitations due to the retrospective nature of the self-report could have resulted in recall bias.

Perampanel as adjunctive therapy in drug resistant epilepsy in adolescents and children waiting for epilepsy surgery: A multicenter observational study in Thailand.

PURPOSE: To evaluate the effectiveness and tolerability of perampanel (PER) in real-world settings in patients between 1 month and 18 years of age with drug resistant epilepsy (DRE) waiting for epilepsy surgery. METHODS: In this multicenter study, patients between 1 month and 18 years of age with DRE treated with PER between January 2020 and June 2021 were selected. The study outcome was effectiveness of PER treatment reported as reduction in seizure frequency and seizure freedom rate. Effectiveness was assessed at 30, 60, 90, 120, 150 and 180 days after initiation of PER. Tolerability profiles were reported as adverse events according to the observations of the patients' family members and physician. RESULTS: Eighty-five patients treated with PER were included in the study. The mean initial dose and mean maximum dose of adjunctive PER was 2 mg/day and 5.8 mg/day, respectively. The mean seizure frequency (rate/week) was 41.3, 25.4, 18.9, 14.3, 11.2, 11.1 and 8.9 seizures at baseline, 30, 60, 90, 120, 150 and 180 days, respectively; the reduction in the mean seizure frequency at all timepoints was significant compared at the baseline (p<0.001). At 180 days, ≥75% seizure reduction was seen in 64.9% (37/57) of the patients and seizure freedom was achieved in 36.8% (21/57). Drowsiness, ataxia, and behavioral changes were the common adverse events observed, and these improved after the dose of PER was reduced. No discontinuation of PER was required due to side effects or intolerance. CONCLUSION: In real-world settings, PER is well tolerated and effective in seizure control in pediatric and adolescent patients with DRE.

Determinants of seizure outcome after resective surgery following stereoelectroencephalography.

OBJECTIVE: The aim of this study was to investigate seizure outcomes after resective epilepsy surgery following stereoelectroencephalography (SEEG), including group characteristics, comparing surgical and nonsurgical groups and assess predictors of time to seizure recurrence. METHODS: Clinical and EEG data of 536 consecutive patients who underwent SEEG at Cleveland Clinic Epilepsy Center between 2009 and 2017 were reviewed. The primary outcome was defined as complete seizure freedom since the resective surgery, discounting any auras or seizures that occurred within the 1st postoperative week. In addition, the rate of seizure freedom based on Engel classification was determined in patients with follow-up of ≥ 1 year. Presumably significant outcome variables were first identified using univariate analysis, and Cox proportional hazards modeling was used to identify outcome predictors. RESULTS: Of 527 patients satisfying study criteria, 341 underwent resective surgery. Complete and continuous seizure freedom after surgery was achieved in 55.5% of patients at 1 year postoperatively, 44% of patients at 3 years, and 39% of patients at 5 years. As a secondary outcome point, 58% of patients achieved Engel class I seizure outcome for at least 1 year at last follow-up. Among surgical outcome predictors, in multivariate model analysis, the seizure recurrence rate by type of resection (p = 0.039) remained statistically significant, with the lowest risk of recurrence occurring after frontal and temporal lobe resections compared with multilobar and posterior quadrant surgeries. Patients with a history of previous resection (p = 0.006) and bilateral implantations (p = 0.023) were more likely to have seizure recurrence. The absence of an MRI abnormality prior to resective surgery did not significantly affect seizure outcome in this cohort. CONCLUSIONS: This large, single-center series shows that resective surgery leads to continuous seizure freedom in a group of patients with complex and severe pharmacoresistant epilepsy after SEEG evaluation. In addition, up to 58% of patients achieved seizure freedom at last follow-up. The authors' results suggest that SEEG is equally effective in patients with frontal and temporal lobe epilepsy with or without MRI identified lesions.

Hypovitaminosis D and risk factors in pediatric epilepsy children.

BACKGROUND: Anti-seizure medication (ASM) treatment is one of the significant risk factors associated with abnormal vitamin D status in epilepsy patients. Multiple studies have shown that adult epilepsy patients can exhibit vitamin D deficiency. However, there are few reports investigating pediatric epilepsy patients. In this study, we aimed to identify risk factors related to hypovitaminosis D in pediatric epilepsy patients in Thailand. METHODS: A cross-sectional retrospective cohort study was conducted in 138 pediatric epilepsy patients who received anticonvulsants from April 2018 to January 2019. Demographic data, seizure types, puberty status, physical activity, duration, and types of anti-seizure medications were analyzed. Patients with abnormal liver function, abnormal renal function, and who received vitamin D supplements or ketogenic diet containing vitamin D were excluded. Levels of serum vitamin D (25(OH)D) were measured. RESULTS: All 138 subjects were enrolled, the age ranged from 1.04 - 19.96 years; (mean = 9.65 ± 5.09), the mean serum 25(OH) D level was 26.56 ± 9.67 ng/ml. The prevalence of vitamin D deficiency was 23.2% and insufficiency was 47.8% respectively. Two risk factors-puberty status (OR 5.43, 95% CI 1.879-15.67) and non-enzyme-inhibiting ASMs therapy (OR 3.58, 95% CI 1.117-11.46)-were significantly associated with hypovitaminosis D, as shown by multivariate analyses. CONCLUSIONS: Our study reports the high prevalence of hypovitaminosis D in pediatric epilepsy patients in Thailand despite being located in the tropical zone. These findings can guide clinicians to measure vitamin D status in pediatric epilepsy patients particularly when they reach puberty and/or are using non-enzyme-inhibiting ASMs therapy. Early detection of vitamin D status and prompt vitamin D supplementation can prevent fractures and osteoporosis later in life. TRIAL REGISTRATION: TCTR20210215005 ( http://www.clinicaltrials.in.th/ ).

Efficacy of oral perampanel in status epilepticus and acute repetitive seizures in children at a tertiary care hospital in Thailand.

Status epilepticus (SE) and acute repetitive seizure (ARS) are emergency conditions associated with significant morbidity and mortality in children. Anti-seizure medications (ASMs) need to terminate seizures to prevent brain damage and death. Common challenges that delay the management of SE and ARS in children at Phramongkutklao hospital are difficulty in accessing intravenous route for drug administration and inadequate number of intensive care units (which will be required in case of the use of adverse events to anesthetic ASMs). Oral, non-sedating ASMs could be a potential option to terminate seizures effectively in SE and ARS in children and further studies in this aspect are needed. We performed a prospective, descriptive study in children with SE or ARS < 18 years of age who had contraindication to or their seizures were refractory to the second-line ASMs after benzodiazepine and received oral perampanel. Demographic data, efficacy, and adverse effects of treatment were recorded. Fifteen patients with SE (13.3%) and acute repetitive seizure (86.6%) were enrolled. All patients received an oral perampanel loading dose and the maintenance dose depended on their body weight. The average loading and maintenance dose were 0.24 mg/kg/dose and 0.12 mg/kg/day, respectively. At 48 h after administration of loading dose of perampanel, eight of fifteen patients (53.3%) became seizure free, one patient had seizure reduction of >75% from baseline, and three patients had seizure reduction of 25-50% from baseline. No serious side effects were observed. These results indicate that oral perampanel may be potential treatment option for SE and ARS in children.

From international guidelines to real-world practice consensus on investigations and management of status epilepticus in adults: A modified Delphi approach.

OBJECTIVE: To establish a consensus which is practical and ready-to-use on investigations (ISE) and for management of status epilepticus (MSE) in adults using a modified Delphi approach. PATIENTS AND METHODS: A 4-round modified Delphi approach was used. First and second rounds were conducted using Google® survey with structured statements and 6-point Likert scale response. Threshold agreement was set to ≥80%. Third round was a face-to-face meeting aimed to facilitate the development of approach algorithms for ISE and MSE. Fourth round was a final review asking participants to rate the algorithms post completion. RESULTS: The panel consisted of 8 board-certified epileptologists along with 6 neurologists from main regional hospitals across Thailand. Thirty-seven statements for ISE and 68 statements for MSE were used for the Round I survey, 17/37 (45.9%) and 49/68 (72.1%) reached threshold agreement (≥80%). The average absolute-agreement intraclass correlation coefficients for ISE and MSE were 0.82 (95% CI 0.71, 0.89) and 0.81 (95% CI 0.73, 0.87), respectively; indicating good extent of consensus among participants. Upon Round II, further 10/18 (55.6%) for ISE and 10/19 (52.6%) for MSE reached agreement. In Round III, face-to-face point-by-point discussion was performed to generate approach algorithms. All (100%) provided positive responses with the algorithms post completion in Round IV. CONCLUSION: A practical and ready-to-use consensus using modified Delphi approach on ISE and MSE was developed in a Thai regional hospital context. In real practice, this approach is more suitable and feasible for a localized setting when compared with totally adopting international guidelines.

A First Case Report of Subependymoma in PTPN11 Mutation-Associated Noonan Syndrome.

Noonan syndrome (NS) is an autosomal dominant disorder in some cases caused by PTPN11 mutations. Since somatic mutations in PTPN11 are seen in several tumor types, NS which causes germline PTPN11 mutations are also increase the risk of hematologic malignancies and brain solid tumors. However, the report of brain tumors in Noonan syndrome remains rather rare. Here, we report the first case of an 11-year-old Thai boy with Noonan syndrome who presented with symptoms related to hydrocephalus secondary to subependymoma in the fourth ventricle, and PTPN11 mutation was identified in this patient.

Effectiveness and Adverse Effect of Intravenous Lacosamide in Nonconvulsive Status Epilepticus and Acute Repetitive Seizures in Children.

Nonconvulsive status epilepticus (NCSE) and acute repetitive seizures (ARS) are associated with significant morbidity and mortality. Due to the lack of randomized-controlled trials of intravenous antiepileptic drugs (AEDs) in these conditions, trials of a new generation of AEDs in this aspect are needed. A prospective interventional study was conducted in children under 18 years of age with NCSE or ARS who either had contraindication to or were refractory to first-line AEDs and received intravenous lacosamide. Demographic data, the efficacy of treatment, and adverse effects were recorded. Eleven patients with a median age of 11 years, predominantly female (72.7%), were enrolled. Average loading dose was 227 mg (8.3 mg/kg/dose) and average daily maintenance dose was 249 mg (4.6 mg/kg/dose). All patients (100%) experienced a reduction in seizure frequency within 24 hours. Eight of eleven patients (72.7%) experienced a reduction in seizure frequency of more than 50% by the end of the study, and one patient became seizure-free. In terms of adverse events, one patient had a bradycardia without prolongation of the PR interval. Interestingly, there was a case of neuronal ceroid lipofuscinosis in which a significant improvement in seizure control was achieved. The results indicate that intravenous lacosamide may be an alternative treatment for NCSE or ARS in children. To our knowledge, this is the first study on the use of intravenous lacosamide in Asian children. This study is registered to Thai Clinical Trials Registry (TCTR) and the trial registration number is TCTR20180508004.

X-Linked Chronic Granulomatous Disease: Initial Presentation with Intracranial Hemorrhage from Vitamin K Deficiency in Infant.

Vitamin K deficiency bleeding (VKDB) is a life-threatening condition and can be found in children as early as neonatal period with early onset intracranial hemorrhage (ICH). Here, we reported a 1-year-old boy who initially presented with intracranial hemorrhage secondary to vitamin K deficiency since 3 months of age and later found to have XL-CGD which was complicated by malabsorption due to severe vaccine-associated mycobacterial disease.