Interventions to promote medication adherence among children with epilepsy: An integrative review.

PROBLEM: Many children with epilepsy face challenges in adhering to their medication, leading to inadequate seizure control. However, the most effective intervention is still unclear. This integrative review's main goal was to examine and synthesize the existing literature on interventions for promoting medication adherence in children with epilepsy. ELIGIBILITY CRITERIA: This integrative review followed Whittemore and Knafl's five-stage framework. Four electronic databases (PubMed, ScienceDirect, Scopus, and CINAHL Complete) were systematically searched from 2013 until 2024 to identify eligible studies published in the English language. The key search terms included "Children with epilepsy" AND "medication adherence" AND "intervention." Studies reporting on the implementation and evaluation of medication adherence interventions in children with epilepsy were eligible. Quality assessment and narrative synthesis were subsequently undertaken. SAMPLE: A total of 17 studies were included in the review. RESULTS: Five interventions were found, including educational, behavioral, and mixed intervention types, using technology and family involvement. Promoting medication adherence is crucial, but tailored interventions for different age groups and sustained support are needed. CONCLUSIONS: Promoting medication adherence is of utmost importance to enhance the knowledge of children who have epilepsy and their families, and to increase medication adherence. However, there is still a need to develop interventions that are appropriate for children of different ages and their families, which should be suitable and sustainable during treatment. IMPLICATIONS: Pediatric nurses should consider socioeconomic factors, ethnicity, family functioning, and parental distress. Strategies include monitoring adherence, continuous communication, and technology support for children with epilepsy during treatment.

Can knowledgeable experts assess costs and outcomes as if they were ignorant? An experiment within precision medicine evaluation.

OBJECTIVES: The purpose of this study is to evaluate the validity of the standard approach in expert judgment for evaluating precision medicines, in which experts are required to estimate outcomes as if they did not have access to diagnostic information, whereas in fact, they do. METHODS: Fourteen clinicians participated in an expert judgment task to estimate the cost and medical outcomes of the use of exome sequencing in pediatric patients with intractable epilepsy in Thailand. Experts were randomly assigned to either an "unblind" or "blind" group; the former was provided with the exome sequencing results for each patient case prior to the judgment task, whereas the latter was not provided with the exome sequencing results. Both groups were asked to estimate the outcomes for the counterfactual scenario, in which patients had not been tested by exome sequencing. RESULTS: Our study did not show significant results, possibly due to the small sample size of both participants and case studies. CONCLUSIONS: A comparison of the unblind and blind approach did not show conclusive evidence that there is a difference in outcomes. However, until further evidence suggests otherwise, we recommend the blind approach as preferable when using expert judgment to evaluate precision medicines because this approach is more representative of the counterfactual scenario than the unblind approach.

Association of HLA genotypes with phenobarbital hypersensitivity in children.

OBJECTIVE: Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes (MPs) to severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drug hypersensitivity has been demonstrated to be associated with variations in the HLA genotypes. This study was to investigate the association between the variations of HLA genotypes and phenobarbital hypersensitivity in Thai children. METHODS: The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included SCARs and MPs. The control patients were Thai children of a corresponding age who had taken phenobarbital for at least 12 weeks without any hypersensitivity reaction. Blood samples were collected for HLA genotyping by using a reverse-sequence-specific oligonucleotide (SSO) probes method. The carrier rates of HLA alleles were compared between 47 cases (27 SCARs and 20 MPs) and 54 controls. RESULTS: The carrier rates of HLA-A*01:01 and HLA-B*13:01 were significantly higher in the phenobarbital-induced SCARs than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [OR] 11.66, 95% confidence interval [CI] 1.21-578.19; 37.04% vs. 11.11%, p = 0.009, OR 4.60, 95%CI 1.29-17.98). There was a trend of a higher carrier rate of HLA-C*06:02 in the phenobarbital-induced SCARs when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, OR 3.31, 95% CI 0.88-13.31). In contrast to the phenobarbital-induced SCARs, only the HLA-A*01:01 carrier rate in the phenobarbital-induced MPs was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, OR 12.69, 95% CI 1.15-661.62). SIGNIFICANCE: An association between phenobarbital hypersensitivity and HLA-A*01:01 and HLA-B*13:01 has been demonstrated in Thai children.

Deep Brain Stimulation of Anterior Thalamic Nuclei for Intractable Epilepsy in Thailand: Case Report

Neurostimulation can be an alternative treatment for medically intractable epilepsy, especially when the resective surgery could not be performed. The author reported a case of 19-year-old, right-handed male patient who had a history of intractable epilepsy for 11 years after post viral encephalitis associated with status epilepticus. Following the failure of antiepileptic medications and then resective surgery, anterior thalamic deep brain stimulation (DBS) was performed. Indirect targeting of anterior thalamic nuclei could not be used because of asymmetric brain shift from prior multilobar resections. Direct targeting of anterior thalamic nuclei from MRI T1 sequence, Short Tau Inversion Recovery (STIR) sequence combined neurophysiological mapping by microelectrode recording were used as a technique for implantation of DBS electrodes. The stimulation was turned on with 145 Hz, pulse width 90 microseconds, 5 volts with cycling mode 1 minute "on" and 5 minutes "0ff". The antiepileptic medications continued the same as pre-operative state. Sixty percent seizure reduction was achieved in 24 months after surgery. There were no side effects of DBS during the follow-up period. Anterior thalamic DBS can be performed safely with satisfactory seizure outcomes. Direct targeting of anterior thalamic nuclei combination with microelectrode recording can be very helpful, especially when asymmetric basal ganglion structures were detected.

Infectious causes of encephalitis and meningoencephalitis in Thailand, 2003-2005.

Acute encephalitis is a severe neurologic syndrome. Determining etiology from among ≈100 possible agents is difficult. To identify infectious etiologies of encephalitis in Thailand, we conducted surveillance in 7 hospitals during July 2003-August 2005 and selected patients with acute onset of brain dysfunction with fever or hypothermia and with abnormalities seen on neuroimages or electroencephalograms or with cerebrospinal fluid pleocytosis. Blood and cerebrospinal fluid were tested for >30 pathogens. Among 149 case-patients, median age was 12 (range 0-83) years, 84 (56%) were male, and 15 (10%) died. Etiology was confirmed or probable for 54 (36%) and possible or unknown for 95 (64%). Among confirmed or probable etiologies, the leading pathogens were Japanese encephalitis virus, enteroviruses, and Orientia tsutsugamushi. No samples were positive for chikungunya, Nipah, or West Nile viruses; Bartonella henselae; or malaria parasites. Although a broad range of infectious agents was identified, the etiology of most cases remains unknown.

Association analysis of CYP2C9*3 and phenytoin-induced severe cutaneous adverse reactions (SCARs) in Thai epilepsy children.

CYP2C9 is the key enzyme in aromatic antiepileptic drugs (AEDs) metabolism. CYP2C9*3 is a loss of function polymorphism. This study was designed to investigate genetic association between CYP2C9*3 and aromatic AED-induced severe cutaneous adverse reactions (SCARs) in Thai children. The 37 aromatic AED-induced SCARs patients (20 phenobarbital and 17 phenytoin) and 35 tolerances (19 phenobarbital and 16 phenytoin) were enrolled. CYP2C9*3 was genotyped by allele-specific PCRs. The association between CYP2C9*3 with phenytoin-induced SCARs and phenobarbital-induced SCARs were analyzed in comparison with tolerances and healthy samples. Significant association between phenytoin-induced SCARs and CYP2C9*3 was discovered (odds ratio=14.52; 95% confidence interval (CI)=1.18-∞, P-value=0.044). CYP2C9*3 was not associated with phenobarbital-induced SCARs. This study is the first report of CYP2C9*3 association to phenytoin-induced SCARs in Thai epileptic children. The CYP2C9*3 is a reasonable predictive genetic marker to anticipate SCARs from phenytoin.

Global fibrinolytic activity, PAI-1 level, and 4G/5G polymorphism in Thai children with arterial ischemic stroke.

BACKGROUND: Prolonged euglobulin clot lysis time (ECLT) and increased level of plasminogen activator inhibitor-1 (PAI-1) were reported to be risk factors of arterial ischemic stroke (AIS) by some studies; however, these findings were not supported by other studies. The objective of this study was to determine the association of ECLT, PAI-1 level, and polymorphisms of 4G and 5G of PAI-1 gene to the development of AIS in Thai children. METHODS: This study included patients aged 1-18 years old. Diagnosis of AIS was confirmed by imaging study. The control group was age- and sex-matched healthy subjects. Demographic data were recorded, and blood was tested for ECLT, PAI-1 level, lipid profiles, fasting blood sugar (FBS), and 4G and 5G polymorphisms of PAI-1 gene. RESULTS: There were 70 subjects participating in this study, consisting of 30 patients and 40 controls. Demographic data, lipid profiles, and FBS were similar between the 2 groups. Furthermore, ECLT and PAI-1 level did not differ between patient and control groups; however, both showed significant correlation (r = .352, P = .006). The 4G/5G polymorphism was the most common genotype in both patient and control groups (69.0% vs. 80.0%). However, 4G and 5G polymorphisms of PAI-1 gene did not correlate with PAI-1 level in this study (P = .797). CONCLUSIONS: The PAI-1 level and 4G/5G polymorphism may not be a risk factor of AIS in this population. It was also found that the 4G/5G polymorphism was the most common PAI-1 genotype in this study.

Phenobarbital-induced severe cutaneous adverse drug reactions are associated with CYP2C19*2 in Thai children.

BACKGROUND: Aromatic anticonvulsant-induced severe cutaneous adverse drug reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), are fatal immune-mediated adverse drug reactions. CYP2C19, a cytochrome P450 isoform, plays a role in metabolic rate of aromatic anticonvulsant. HLA-B*1502 has also been demonstrated to be associated with carbamazepine-induced SJS-TEN. METHODS: Forty case patients who were diagnosed with SCARs after initiation of phenobarbital (PB), phenytoin (PHT), or carbamazepine (CBZ) for 1-8 wk and forty control patients who received PB, PHT, or CBZ at least 2 months with no adverse drug reactions were enrolled in the study. The genotypes of CYP2C19*1, CYP2C19*2, and HLA-B*1502 were analyzed using allele-specific polymerase chain reaction technique. Clinical characteristics of SCARs patients who used different drugs were also analyzed. RESULTS: There was no significant difference in sex, onset of symptoms, laboratory results, treatment, and length of stay among patients with SCARs due to PB, PHT, or CBZ. The patients with CYP2C19*2 variant had a trend to have a likelihood to develop SCARs more than the patients with CYP2C19 wild type (OR = 2.5, 95% CI (0.96-67.3) p = 0.06). In subgroup analysis, the patients with CYP2C19*2 variant were at four times increased risk of SCARs from phenobarbital more than the patients with CYP2C19 wild type (OR = 4.5, 95% CI (1.17-17.37) p < 0.03). There was no association between the HLA-B*1502 and aromatic anticonvulsant-induced severe cutaneous adverse reactions (SCARs). CONCLUSION: CYP2C19*2 variant may play a role in the genetic predisposition of SCARs from phenobarbital.

Apparent diffusion coefficients in evaluation of pediatric brain tumors.

BACKGROUND: MRI, which has high sensitivity in brain tumor detection, cannot reliably determine tumor grading or histology. Diffusion-weighted imaging and apparent diffusion coefficients (ADCs) provide information of tumor cellularity that can correlate with grading. OBJECTIVE: To investigate ADCs in differentiation low-grade from high-grade pediatric brain tumors. MATERIAL AND METHOD: Preoperative MRI, DWI, and ADC images of pediatric patients with pathologically proven brain tumors were retrospectively reviewed at a university hospital in two-year periods and classified into low-grade and high-grade categories. Regions of interest were placed manually at the center and periphery of the solid tumor regions, then ADC values were calculated at "b" values = 0, 1000 sec/mm2. RESULTS: The ADC values were calculated in 15 patients, which included 12 males and three females with an age range from three to 14 years. Seven and eight were with low- and high-grade tumors respectively. The ADC values of low-grade tumors were markedly higher than those of high-grade tumors with statistically significant differences by all methods of measurements at the central peripheral, and average areas on Man-Whitney U test, with p-values of 0.037, 0.009, and 0.021, respectively. CONCLUSION: MRI with ADCs for preoperative pediatric tumor evaluation may be useful for predicting tendency of tumor grading and surgical planning.

Proteomic analysis reveals plasma haptoglobin, interferon-γ, and interleukin-1ß as potential biomarkers of pediatric refractory epilepsy.

BACKGROUND: Children with refractory epilepsy (RE) are associated with increased mortality rate, nonfatal injuries, disability, and diminished quality of life. Biomarkers for the early prediction of RE is still an unmet need. METHODS: Eighteen children with RE and six age-matched unrelated controls were included in this study. Plasma samples were prefractionated by the optimized thermal treatment before proteomic analysis using 2DE-LC-MS/MS. Bioinformatic analysis was carried out using STRING protein network. Immunoassay of unprocessed plasma was applied to confirm changes of proteins of interest. P-value < 0.05 was considered statistically significant. RESULTS: Proteomic analysis (n = 6 each group) revealed nine differentially expressed proteins, i.e., haptoglobin, S100A9, serpin B1, apolipoprotein A-I, apolipoprotein A-IV, apolipoprotein C-II, alpha-1-acid glycoprotein 1 and 2, and transthyretin. Western immunoblotting confirmed haptoglobin upregulation in the RE group. STRING protein network predicted the inflammatory cytokines, i.e., interferon gamma (IFN-γ), interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α), play roles in pathophysiology in RE patients. Cytokine immunoassay (n = 24, 18 RE vs. 6 controls) exhibited plasma IFN-γ was upregulated in RE patients as compared to the healthy individuals (median [IQR]; 2.9 [2.9, 4.9] vs. 1.32 [0.8, 1.5] pg/mL, p = 0.0013), and plasma IL-1ß was significantly downregulated in patients (1.0 [0.2, 1.9] vs. 4.5 [1.9, 11.0] pg/mL, p = 0.01). TNF-α had no difference between groups. The results suggest that haptoglobin may be associated with oxidative brain damage, while IFN-γ and IL-1ß may be involved with neuroinflammation. CONCLUSIONS: Alterations in plasma haptoglobin, IFN-γ, and IL-1ß were associated with RE patients. Future studies using a combination of these candidate biomarkers may help predict the intractability of epilepsy in pediatric populations.

Headache in junior high school students: types & characteristics in Thai children.

OBJECTIVE: To survey the prevalence, types, and characteristics of headache in junior high school students. MATERIAL AND METHOD: A two-stage study was conducted in seventh grade students in Bangkok, Thailand. A screening self-administered check-list questionnaire and a face-to-face interview followed by physical examination were performed. Headache was diagnosed and classified according to the Second Edition of the Classification of Headache Disorder criteria. RESULTS: 953 students (448 boys and 505 girls, mean-age 13.2 years) in seventh grade, participated in the present study. Eight hundred thirty three students (87.4%) reported of having five episodes of headache in the past three months. After person-to-person interview; there were 121 (12.6%), 116 (12.1%), nine (0.9%), and seven (0.7%) students who had headache attributing to rhinosinusitis/upper respiratory tract infections, migraine, nonspecific headache with upper-limit systolic blood pressure, and tension-type headache respectively. Lack of sleep and stress related to daily school-activities were reported as headache precipitator in 25 and 23 students with migraine, respectively. School absenteeism was documented in four students with migraine. Only one student received migraine prophylactic treatment. CONCLUSION: Headache was common in Thai grade seven schoolchildren. Awareness of its high prevalence in these age-group children will lead to early identification of students who may need intervention and specific treatment.

Cost-effectiveness analysis of epilepsy surgery in children and adolescents with drug resistant focal epilepsy at three years in a tertiary care epilepsy center in Thailand.

Epilepsy surgery is proven as a cost-effective treatment in developed countries, especially in adults with drug resistant epilepsy (DRE). This study is aimed to demonstrate the cost-effectiveness of epilepsy surgery in children and adolescents with DRE at three years compared with those who were eligible for surgery but received medical treatment. This study was conducted from January 2014 to December 2018. Clinical data were obtained from a retrospective chart review. Direct medical costs, including epilepsy surgery, inpatient and outpatient treatment were retrieved from the finance department. Direct non-medical costs were collected from the family interview. The effectiveness was determined by percent seizure reduction and quality of life assessed by EQ-5D scores. Decision tree analysis using TreeAge Pro® 2018 was deployed to determine the cost-effectiveness. Seventeen patients had epilepsy surgery and 19 were in the medical group. Seizure freedom was noted in 52% and 16% in the surgical and medical groups, respectively. Incremental cost-effectiveness ratio (ICER) was 743,040 THB (22,793 USD) per 1 QALY and 3302 THB (101 USD) per 1% seizure reduction. The study did not demonstrate cost-effectiveness of epilepsy surgery in the short term compared with Thailand's threshold (160,000 THB (4908 USD) per 1 QALY). Epilepsy surgery may be cost-effective if evaluated beyond three years.

Delayed cortical maturation at the centrotemporal brain regions in patients with benign childhood epilepsy with centrotemporal spikes (BCECTS).

Benign childhood epilepsy with centrotemporal spikes (BCECTS) is an epilepsy syndrome commonly found in child and adolescent. Although the prognosis is mostly favorable as long as the seizure is well controlled. However, they are often suffering from the cognitive and behavioral problems which might be the consequences of the initial insults. It is still not clear whether the initial epileptiform discharges has long term impact on the resting-state brain activities at later ages. This study investigated the resting-state brain activities in BCECTS patients with clinical seizure remission stage (n = 16; 11 males) and compared with the non-epileptic, age-matched control subjects. Quantitative electroencephalography (qEEG) revealed a significantly higher absolute power of the theta and alpha waves in BCECTS patients with clinical seizure remission as compared with the non-epileptic control subjects. Interestingly, the differences were observed mainly over the centrotemporal electrodes which are the common sites of the initial epileptiform discharges. The differences were more significant in patients with bilateral epileptiform discharges than those with the unilateral epileptic activities. Typically, the brain wave power continuously decreases with increasing ages. Therefore, higher absolute powers of the brain waves indicate more delayed in cortical maturation compared with the non-epileptic control group. These findings indicated that BCECTS patients have delay cortical maturation at the centrotemporal brain regions even at the clinical seizure remission phase.

Underutilization of epilepsy surgery in ASEAN countries.

PURPOSE: This survey was performed to determine the availability of epilepsy surgery, and understand the limiting factors to epilepsy surgery in ASEAN countries with total of 640 million population. METHOD: A cross-sectional survey was completed by national representatives in all ASEAN countries (Brunei, Cambodia, East Timor, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam). RESULTS: Overall facilities for initial epilepsy pre-surgical evaluation are available in most countries, but further non-invasive and invasive investigations are limited. Three countries (Brunei, Cambodia, and East Timor) have no epilepsy center, and 2 countries (Laos, Myanmar) have level 2 centers doing tumor surgery only. Level-3 epilepsy centers are available in 6 countries (Indonesia, Malaysia, Philippine, Singapore, Thailand, Vietnam); only 5 countries (Indonesia, Malaysia, Philippine, Singapore, Thailand) has at least one level-4 epilepsy care facility. Indonesia with 261 million population only has one level 3 and another level 4 center. The costs of presurgical evaluation and brain surgery vary within and among the countries. The main barriers towards epilepsy surgery in ASEAN include lack of expertise, funding and facilities. CONCLUSIONS: Epilepsy surgery is underutilized in ASEAN with low number of level 3 centers, and limited availability of advanced presurgical evaluation. Lack of expertise, facilities and funding may be the key factors contributing to the underutilization.

Favorable response of intraommaya topotecan for leptomeningeal metastasis of neuroblastoma after intravenous route failure.

A 3-year-old male, diagnosed with stage 4 neuroblastoma, developed recurrent leptomeningeal metastasis after multi-modality treatment including multi-agent chemotherapy, surgery, high dose chemotherapy plus stem cell rescue, cis-retinoic acid and intravenous (IV) topotecan. He then received intraommaya (IO) topotecan three times weekly (maximum dose; 0.4 mg). A complete response was achieved by a resolution of malignant cells in cerebrospinal fluid and resolution leptomeningeal enhancement by brain MRI. Treatment toxicities included low-grade fever and minimal headache. The duration of treatment response from IO topotecan was 18 weeks. The survival time from CNS recurrence in this patient was 13 months. We suggest IO topotecan be considered for neoplastic meningitis of tumors with known sensitivity to topotecan.

Clinical course and long-term outcome in children with alteration of consciousness underwent continuous EEG monitoring: A prospective observational study in Thailand.

The study aims to explore the clinical course and long-term outcome in children with altered consciousness who underwent cEEG monitoring. A prospective observational study was conducted in neonatal and pediatric intensive care units from 1 September 2014 through 31 March 2017. Standard 10-20 cEEG monitoring was applied. Twenty children were included in this study. Their ages ranged from 1 day to 142.7 months (median age 40.6 months). Continuous EEG was commenced from 5 h to 5 days after the onset of alteration of consciousness (median 40.2 h). The range of EEG monitoring duration was 6.7-256.3 h (mean 50.4 h). Four patients (20%) had preexisting neurological diseases, which were 2 epilepsy, adrenoleukodystrophy and unknown cause of brain atrophy. Eleven patients (55%) had principle neurological diagnosis and the others 9 (45%) had systemic illnesses. Sixteen patients (80%) had clinical seizures prior to the commencement of cEEG monitoring. Fifteen patients (75%) received antiepileptic drugs before cEEG monitoring. NCSE was diagnosed in 25%. Comparison of patients' characteristics and long-term outcome between the NCSE and non NCSE groups, there was statistical significance between the two groups only with respect to epileptiform discharges. The patients are being follow up for a period of 24 months after the end of cEEG monitoring. The outcome of patients divided into those with a favorable outcome and those with poor outcome according to modified Rankin scale. The patients with isoelectric EEG background had relatively poorer outcomes than those with normal or slow background activities. The overall mortality rate for the entire population was 15%.

Juvenile Ocular Myasthenia Gravis: Presentation and Outcome of a Large Cohort.

BACKGROUND: Isolated ocular myasthenia gravis (MG) is sparingly common in children relative to adults, ranging from 71% to 93% of all children with MG. PURPOSE: We aimed to characterize the ocular manifestations and outcomes in children with isolated ocular MG. METHODS: Medical records of consecutive 62 subjects less than 15 years of age with ocular MG, were retrospectively reviewed. Demographic data, presenting ocular features, types and variabilities of duction limitation, MG confirmatory tests, types of and responses to treatment, and generalized MG conversion were reviewed. RESULTS: Mean age at onset and follow-up time were 49 months (range, one to 173 months) and 95 months (range, six to 226 months), respectively. Female-to-male ratio was 1.5:1. Initially, ptosis was found in 60 subjects (96.8%), while duction limitation was observed in 28 subjects (45.2%). Total ophthalmoparesis was the most common type of duction limitation. Variability of duction limitation was found in 68% of subjects during the follow-up. Pyridostigmine alone was the most common medication used (48.4%); ptosis was more responsive to therapy than duction limitation. Conversion to generalized MG occurred in 19.4% of subjects, with a mean interval to conversion of nine months after symptom onset. Most conversions (91.7%) occurred in the first two years. CONCLUSIONS: Ptosis was more responsive to treatment than duction limitation. Thus other treatment modalities, as well as strabismic amblyopia screening, should be considered in children with prolonged duction limitation that is refractory to medication. In contrast with adults, a much lower proportion of children converted to generalized MG. This may explain the higher prevalence of isolated ocular MG among the juvenile population.

R147W in PROC Gene Is a Risk Factor of Thromboembolism in Thai Children.

The p.R147W mutation, the c.C6152T in exon 7, causing a change in amino acid from arginine to tryptophan of the PROC gene has been reported as a common mutation in Taiwanese populations with venous thromboembolism (VTE). The present study aimed to identify the prevalence of p.R147W in the Thai population and children with TE and the risk of developing TE. Patients aged ≤18 years diagnosed with TE were enrolled. The PROC gene was amplified by polymerase chain reaction using a specific primer in exon 7. The restriction fragment length polymorphism was designed using MwoI restriction enzyme. A total of 184 patients and 690 controls were enrolled. The most common diagnosis of TE was arterial ischemic stroke (AIS), at 100 (54.3%), followed by VTE, at 38 (20.6%), and cerebral venous sinus thrombosis (CVST), at 23 (12.5%). The prevalence of heterozygous and homozygous p.R147W in patients and controls was 9.5% versus 5.8% and 2.7% versus 0.1%, respectively. Heterozygous p.R147W had odds ratios (ORs) of 1.8 (95% confidence interval [CI]: 1.0-3.2, P = .04), 3.2 (95% CI: 1.2-8.2, P = .009), and 4.5 (95% CI: 1.6-12.8, P = .002) of developing overall TE, VTE, and CVST, respectively. Homozygous p.R147W had ORs of 20.2 (95% CI: 2.3-173.7, P < .001), 21.4 (95% CI: 2.2-207.9, P < .001), and 43.3 (95% CI: 3.8-490.6, P < .001) of developing overall TE, AIS, and CVST, respectively. This study suggested that p.R147W is a common mutation and increased risk of TE in Thai children.

Determination of plasma Levetiracetam level by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS-MS) and its application in pharmacokinetics studies in neonates.

BACKGROUND: Levetiracetam (LEV) is an antiepileptic drug which has good safety and efficacy in neonatal seizure (NS), a common incident in neonates with weight <1500 g. The pharmacokinetics for LEV in neonatal populations is yet to be clearly understood. In this study, we developed and validated a method for determination of LEV in plasma by liquid chromatography tandem mass spectrometry for the purpose of pharmacokinetic study. METHODS: Plasma LEV was spiked with Lamivudine as internal standard before extraction by C18 solid-phase extraction (SPE) cartridge. Chromatography was performed using isocratic elution with mobile phase A: B (10: 90) for 2.0 min with flow rate 0.4 mL/min. The mobile phase was composed of 0.1% formic acid in 10.0 mM ammonium acetate (A) and 100% methanol (B). The injection volume was 1.0 µL and the total run time was 2.0 min. Multiple reaction monitoring (MRM) with electro spray in positive mode was used. The mass transition for LEV was 171.2/126.0 and 230.0/112.0 for IS with retention time of 0.73 and 0.72 min, respectively. RESULTS: A calibration curve range from 0.50-80.0 µg/mL was obtained with a correlation coefficient >0.99 in the quadratic model. Precision and accuracy was within the acceptable range and the intra- and inter-day %CV for three concentrations of QCs were <10%. CONCLUSION: This method was reliable, accurate and applicable for LEV pharmacokinetic study in neonates with seizure.

Migraine in Thai children: prevalence in junior high school students.

A cross-sectional study to determine the prevalence of migraine in seventh grade Thai students in 4 junior high schools in Bangkok, Thailand, according to the diagnostic criteria of the second edition of the Classification of Headache of the International Headache Society was conducted in July 2004. The study included a screening self-administered questionnaire and face-to-face interview with physical examination. The diagnosis of migraine was made and confirmed by 2 pediatric neurologists. All of 1789 students in participating schools completed the questionnaire. After 2 interviews, 248 students (13.8%) were diagnosed with migraine. The prevalence in girls was higher than that in boys (16.2% vs 11.7%). Migraine as having aura was diagnosed in 34 students (13.7%). One student had sporadic hemiplegic migraine. Among 248 children, 176 (71%) reported the duration of headache between 1 and 2 hours. The leading precipitating factor of migraine was the stress related to daily school activities (17.7%). There were 32 students (12.9%) with frequent and intense headache who were referred to their primary physicians for further management. This study had disclosed a high prevalence of migraine in seventh grade Thai students in Bangkok City and reflected the existing burden of this illness in Thai students.