Frequent Unrecognized Vertebral Fractures Associated with Increased Body Fat Mass in Children and Adolescents with Duchenne Muscular Dystrophy.

OBJECTIVE: Patients with Duchenne muscular dystrophy (DMD) have an increased risk of vertebral fractures (VFs). Ethnic variations may partly contribute to the fracture risk. This study aimed to demonstrate the VFs and body fat mass in Asian patients with DMD. METHODS: Demographic data and DMD-related parameters of the enrolled patients were collected. Lateral thoracolumbar spine radiographs were performed for VF assessment. The Genant classification was applied for VF severity grading (mild, moderate, and severe). Body composition analysis using dual-energy X-ray absorptiometry was performed. Serum calcium, phosphate, intact parathyroid hormone, and 25-hydroxyvitamin D concentrations were determined. RESULTS: There were 25 children and adolescents with DMD enrolled. The median (interquartile range [IQR]) age was 12.9 (9.6-19.3) years. Nine patients (36%) had VFs with a total of 31 sites of VFs (mild, N = 10; moderate, N = 3; and severe, N = 18). These VFs had never been recognized prior to this study. Comparing with the non-VF group, the VF group received a significantly greater cumulative prednisolone equivalent dose (1,258 [948-1,664] vs. 291 [17-823] mg/kg, p = 0.003). Body fat mass, represented by fat mass index and body fat percentage Z-scores, was greater in the VF group (2.46 [2.21-2.51] vs. 1.63 [0.36-2.07], p = 0.011 and 4.4 [3.1-5.5] vs. 1.8 [0.6-3.5], p = 0.008, respectively). No differences in serum calciotropic hormones and vitamin D status were demonstrated between patients with and without VFs. CONCLUSIONS: VFs were frequent in patients with DMD. Patients with VFs had greater cumulative glucocorticoid dose and body fat mass than those without VFs.

Sleep Disorder: An Overlooked Manifestation of Glucose Transporter Type-1 Deficiency Syndrome.

Glucose transporter type-1 deficiency syndrome (Glut1 DS) is a rare disorder with various manifestations. Early diagnosis is crucial because treatment with the ketogenic diet can lead to clinical improvement. Here, we report the cases of two siblings with Glut1 DS and one of them presented with sleep disorder which is a rare and atypical manifestation of Glut1 DS. Patient 1 was a 3.5-year-old boy who presented with paroxysmal loss of tone and weakness of the whole body with unresponsiveness after waking up. He also had excessive daytime sleepiness, insomnia, and restless sleep. His other clinical findings included focal seizures, paroxysmal exercise-induced dyskinesia (PED), ataxia, mild global developmental delay, and hyperactivity. Patient 2 was a 5.5-year-old boy who presented with drug-resistant focal epilepsy, global developmental delay, paroxysmal dystonia, and ataxia. A novel heterozygous nonsense variant of SLC2A1, c.1177G > T (p.Glu393*), classified as a pathogenic variant, was identified in both patients, but not in their parents' blood. After treatment with the modified Atkins diet, their neurological functions significantly improved. In conclusion, we reported two siblings with variable phenotypes of Glut1 DS with a novel nonsense mutation. Although sleep disorder and daytime somnolence were the nonclassical manifestations of Glut1 DS, the diagnostic evaluation of possible Glut1 DS in patients presented with daytime sleepiness, particularly in cases with the cooccurrence of seizures or movement disorders should be considered.

Successful endovascular treatment of pediatric basilar infectious (mycotic) aneurysm: a case report and review of the literature.

BACKGROUND: Intracranial infectious aneurysms are rarely reported in children; in particular, they are very rare in infants. They are mostly related to infective endocarditis and are usually located in the anterior cerebral vasculature. A ruptured intracranial infectious aneurysm is a catastrophic event associated with high morbidity and mortality rates. CASE REPORT: An 8-month-old female infant presented with a prolonged fever without any organ-specific symptoms. Two weeks after admission, she had a high-grade fever with drowsiness; the cerebrospinal fluid (CSF) examination indicated meningitis. Despite treatments with empiric antibiotic and antiviral agents, both her condition and the repeated CSF profiles worsened. The ineffective medications were promptly changed to susceptible antibiotic after the CSF culture showed Pseudomonas aeruginosa. Three days after the diagnosis of meningitis, the patient suddenly developed seizures and alteration of consciousness. The computerized tomography and angiography (CT and CTA) of the brain demonstrated a diffuse subarachnoid hemorrhage (SAH) with intraventricular hemorrhage (IVH) and a lobulated fusiform aneurysm at the proximal basilar artery, suggestive of a ruptured basilar infectious aneurysm. Endovascular treatment was planned and a transarterial occlusion of the vertebrobasilar junction was performed in order to disrupt inflow of the aneurysm. After endovascular intervention, her clinical symptoms gradually improved and the patient was discharged after completing a 4-week course of antibiotics. At the 6-week follow-up, she was doing well without neurological deficit. CONCLUSION: To our knowledge, this is the first reported case of a ruptured basilar infectious aneurysm in an infant secondary to Pseudomonas meningitis, successfully treated with parent artery occlusion.

Effectiveness of neurofeedback versus medication for attention-deficit/hyperactivity disorder.

BACKGROUND: Neurofeedback (NF) is an operant conditioning procedure that trains participants to self-regulate brain activity. NF is a promising treatment for attention-deficit/hyperactivity disorder (ADHD), but there have been only a few randomized controlled trials comparing the effectiveness of NF with medication with various NF protocols. The aim of this study was therefore to evaluate the effectiveness of unipolar electrode NF using theta/beta protocol compared with methylphenidate (MPH) for ADHD. METHODS: Children with newly diagnosed ADHD were randomly organized into NF and MPH groups. The NF group received 30 sessions of NF. Children in the MPH group were prescribed MPH for 12 weeks. Vanderbilt ADHD rating scales were completed by parents and teachers to evaluate ADHD symptoms before and after treatment. Student's t-test and Cohen's d were used to compare symptoms between groups and evaluate the effect size (ES) of each treatment, respectively. RESULTS: Forty children participated in the study. No differences in ADHD baseline symptoms were found between groups. After treatment, teachers reported significantly lower ADHD symptoms in the MPH group (P = 0.01), but there were no differences between groups on parent report (P = 0.55). MPH had a large ES (Cohen's d, 1.30-1.69), while NF had a moderate ES (Cohen's d, 0.49-0.68) for treatment of ADHD symptoms. CONCLUSION: Neurofeedback is a promising alternative treatment for ADHD in children who do not respond to or experience significant adverse effects from ADHD medication.

1q21.3 deletion involving GATAD2B: An emerging recurrent microdeletion syndrome.

GATAD2B gene is involved in chromatin modification and transcription activity. Loss-of-function mutations of GATAD2B have recently been defined to cause a recognizable syndrome with intellectual disability (ID). Human TPM3 gene encoding thin filament protein is associated with myopathies. Both genes are located on chromosome 1q21.3. We herein report an infant with feeding difficulty, developmental delay, hypotonia, and dysmorphic features including small palpebral fissures, telecanthus, sparse hair and eyebrow, cup-shaped ears, and clinodactyly. Karyotype was normal. Single nucleotide polymorphism array revealed a 1.06 Mb deletion of chromosome 1q21.3, which was confirmed to be de novo. The deleted region encompassed 35 genes, including three known disease-associated genes, namely GATAD2B, TPM3, and HAX1. We further identify and summarize seven additional patients with 1q21.3 microdeletion from literature review and clinical databases (DECIPHER, ISCA/ClinGen). Genomic location analysis of all eight patients revealed different breakpoints and no segmental duplication, indicating that non-homologous end joining is a likely mechanism underlying this particular microdeletion. This data suggests that 1q21.3 microdeletion is a recurrent microdeletion syndrome with distinguishable phenotypes, and loss of function of GATAD2B is the major contributor of the characteristic facies and ID. Additionally, the deletion of TPM3 warrants a risk of concomitant muscle disease in our patient. © 2017 Wiley Periodicals, Inc.

Successful Treatment of Large Occipital Encephalocele Presenting with Bilateral Vocal Cord Paralysis: A Case Report.

large subtorcular occipital encephalocele in neonate carries higher risk of associated hindbrain anomalies and secondary process for neurological deterioration which predict the surgical outcomes and long-term prognosis. The dysfunction of the lower cranial nerves often leads to worsening of neurological status from poor respiratory function and repeated aspiration pneumonia. The aims of repairing encephalocele include a good closure of the defect, preservation or restoration of neurological functions and better cosmetic results. The author presented a successful surgical strategy for management of a 4-month-old infant with a large subtorcular occipital encephalocele presented with bilateral vocal cord paralysis and swallowing dysfunction. A step by step approach unlocked the main mechanism(s) of reversible lower cranial dysfunctions in this specific situation, including the increased intracranial pressure and shifting of the axis of lower brain stem.

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.

Spinal muscular atrophy in an upper-middle-income nation before the advent of reimbursed disease-modifying therapies.

OBJECTIVE: To elucidate the clinical characteristics and standard of care (SoC) of spinal muscular atrophy (SMA) patients in Thailand, focusing on primary endpoints: age at death and a composite of death or tracheostomy need. DESIGN: Retrospective observational study. SETTING: Seven tertiary centres across Thailand. PATIENTS: Records of 110 patients with genetically confirmed SMA, spanning 2012-2021. INTERVENTIONS: Historical data review; no active interventions. MAIN OUTCOME MEASURES: Age at death and a composite measure of death or tracheostomy necessity. RESULTS: The cohort included 1 SMA0, 50 SMA1, 40 SMA2 and 19 SMA3 cases. Median ages at the onset and diagnosis of SMA1 were 3 and 6.2 months. Of SMA1 patients, 63% required ventilators, and eight received dimethyltryptamines (DMTs) at a median of 15 months (range 6.4-24.5 months). The median time from onset to DMT was 11 months (range 4.2-20.5 months). Among SMA1 patients, 73% died by the study's end. SMA2 and SMA3 patients' median onset ages were 11 and 24 months, respectively, with diagnosis at 24.8 and 68.7 months. Half of all types received physical therapy. CONCLUSIONS: Significant delays in diagnosis and SoC access, including DMTs, were observed, underscoring urgent needs for improved diagnostic and care strategies to enhance SMA patient outcomes in Thailand.

Anxiety and Parenting Style in Children and Adolescents With Tic Disorders.

BACKGROUND: To study the associations of parenting styles and anxiety in Thai children and adolescents with tic disorders, comparing with healthy children and adolescents. METHODS: A cross-sectional study of children and adolescents aged between six and 18 years with tic disorders were enrolled. The control group comprised gender- and age-matched healthy children with no history of tic disorders. The Yale Global Tic Severity Scale was used to assess tics severity. All participants were evaluated for anxiety trait and state using the State-Trait Anxiety Inventory for Children (STAIC). The anxiety disorders were screened by using the Screen for Child Anxiety-Related Emotional Disorders questionnaire. Parenting styles were evaluated by the Parenting Styles and Dimensions Questionnaire. RESULTS: A total of 41 children with tic disorders and 41 children in the control group were enrolled. According to the STAIC, the anxiety state and trait scores were significantly higher in the tic disorders group than in the control group (median [interquartile range]: 28 [13 to 31] vs 8 [6 to 10], P≤0.001, and 31 [18 to 36] vs 8 [3 to 11], P≤0.001, respectively). Furthermore, anxiety disorder was more frequently found in children with tic disorders than in controls (58.5% vs 17.1%, P≤0.001). There was no significant correlation between anxiety symptoms, parenting styles, and the severity of tics. CONCLUSION: Anxiety is common in Thai children with tic disorders. Screening for anxiety in children and adolescents with tic disorders is essential, leading to early detection and providing proper management.

Case report: Severe nonketotic hyperglycinemia in a neonate without apparent seizures but concomitant cleft palate and cerebral sinovenous thrombosis.

Nonketotic hyperglycinemia (NKH) is in most cases a fatal inborn error of metabolism which usually presents during the neonatal period as encephalopathy and refractory seizures. The reported congenital anomalies associated with NKH included corpus callosal agenesis, club foot, cleft palate, and congenital heart disease. Here, we report a newborn who presented with encephalopathy without overt seizures, cerebral venous sinus thrombosis, and cleft palate. Electroencephalography showed a burst suppression pattern, which suggests the etiology could be due to a metabolic or genetic disorder. The amino acid analysis of plasma and cerebrospinal fluid showed elevated glycine. Whole exome sequencing identified a heterozygous c.492C > G; p.Tyr164Ter variant in exon 4 of the GLDC gene inherited from the patient's father. Further long-read whole genome sequencing revealed an exon 1-2 deletion in the GLDC gene inherited from the patient's mother. Additional analyses revealed no pathogenic variants of the cleft palate-related genes. The cleft palate may be an associated congenital anomaly in NKH. Regarding cerebral venous sinus thrombosis, we found a heterozygous variant (p.Arg189Trp) of the PROC gene, which is a common cause of thrombophilia among Thai newborns. A neonate with NKH could present with severe encephalopathy without seizures. A close follow up for clinical changes and further next generation sequencing are crucial for definite diagnosis in neonates with encephalopathy of unclear cause.

Sarcoplasmic Myxovirus Resistance Protein A: A Study of Expression in Idiopathic Inflammatory Myopathy.

Background: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune diseases affecting primarily proximal muscles. Major subtypes include dermatomyositis, polymyositis, inclusion body myositis, immune-mediated necrotizing myopathy and antisynthetase syndrome. Overexpression of sarcoplasmic myxovirus-resistance protein A (MxA) has been observed in muscle biopsy specimens of dermatomyositis but is rarely seen in other subtypes of IIM and other myopathies. Objective: We evaluate the expression of sarcoplasmic MxA and its diagnostic value in IIM and other myopathies. Methods: One hundred and thirty-eight muscle biopsy specimens with the diagnosis of IIM and other myopathies from 2011 to 2020 were reviewed and stained for MxA by immunohistochemistry. The difference of the expression of MxA between IIM and other myopathies was analyzed by Fisher's exact test, and the sensitivity and specificity of MxA immunohistochemistry in the diagnosis of IIM were assessed. Results: MxA protein was positive in 16/138 (11.6%) specimens. All 12 dermatomyositis specimens positive for MxA protein were positive in perifascicular area pattern. Only dermatomyositis specimens had a significantly higher percentage of positive sarcoplasmic MxA expression than specimens of other subtypes of IIM (p<0.001). Sarcoplasmic MxA expression for dermatomyositis diagnosis had a sensitivity of 46.15% (95% CI 26.59-66.63%) and a specificity of 94.44% (95% CI 81.34-99.32%) with the positive and negative likelihood ratio of 8.31 (95% CI 2.03-34.01) and 0.57 (95% CI 0.40-0.82), respectively. Conclusion: The MxA immunohistochemistry is highly specific for dermatomyositis and should be added to a routine inflammatory panel of muscle biopsy. MxA expression should be cautiously interpreted to avoid pitfalls.

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.

HLA-DRB1∗1502 Is Associated With Anti-N-Methyl-D-aspartate Receptor Encephalitis in Thai Children.

BACKGROUND: Anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) is one of the most common types of autoimmune encephalitis. Most patients have no apparent immunologic triggers, which suggests a genetic predisposition. This study was conducted to identify human leukocyte antigen (HLA) class II alleles associated with anti-NMDARE in Thai children. METHODS: This case-control study enrolled patients younger than 18 years who were diagnosed with anti-NMDARE between January 2010 and December 2020. A "good outcome" was determined as a patient with a modified Rankin scale score of less than 2 at any follow-up visit. HLA genotypes were determined at four-digit alleles using reverse sequence-specific oligonucleotide probe hybridization. The HLA class II allele frequency in patients was compared with that in a database of 101 healthy control Thai children. RESULTS: Thirty-four patients were enrolled with a mean age of 12.8 ± 5.6 years (females 85.3%). The HLA-DRB1∗1502 allele frequency was significantly higher in patients than in controls (odds ratio, 2.32; 95% confidence interval, 1.11-4.8, P = 0.023). A good outcome was noted in 14 of 14 (100%) HLA-DRB1∗1502-positive patients (median time to a good outcome, 6 months) and 14 of 17 (82.3%) HLA-DRB1∗1502-negative patients (median time to a good outcome, 3 months). Two (11.8%) HLA-DRB1∗1502-positive patients had one relapse each, and six (35.3%) HLA-DRB1∗1502-negative patients had one to three relapses. CONCLUSIONS: HLA-DRB1∗1502 was significantly associated with anti-NMDARE in our patients. Most patients had good outcomes. HLA-DRB1∗1502-positive patients tended to require a longer time to achieve a good outcome but had less frequent relapses than HLA-DRB1∗1502-negative patients.

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.

MOG-IgG- versus AQP4-IgG-Positive Optic Neuritis in Thailand: Clinical Characteristics and Long-Term Visual Outcomes Comparison.

PURPOSE: To compare demographic data, clinical and radiological characteristics, treatment, and long-term visual outcomes between myelin oligodendrocyte glycoprotein autoantibody-positive optic neuritis (MOG-IgG + ON) and aquaporin-4 autoantibody-positive optic neuritis (AQP4-IgG + ON) in Thailand. PATIENTS AND METHODS: We included individuals who were diagnosed with either MOG-IgG + ON or AQP4-IgG + ON over an 11-year period. Demographic data, clinical and radiological characteristics at ON presentation, treatment, and long-term visual outcomes were retrospectively collected. RESULTS: There were 16 patients (28 eyes) and 43 patients (59 eyes) in the MOG-IgG + ON and AQP4-IgG + ON groups, respectively. AQP4-IgG + ON occurred predominantly in female patients whereas MOG-IgG + ON-affected female patients and male patients equally (p < 0.001). Prior or concurrent non-ON demyelinating events were more often observed at AQP4-IgG + ON onset (p < 0.001). At ON presentation, bilaterality and the presence of optic disc edema were predominantly found in the MOG-IgG + ON group (bilaterality: 80% vs 8%, MOG-IgG + ON vs AQP4-IgG + ON patients, respectively (p < 0.001); presence of optic disc edema: 92.3% vs 36.6%, MOG-IgG + ON- vs AQP4-IgG + ON-affected eyes, respectively (p < 0.001)). There was no statistically significant difference in age at ON onset, nadir visual acuity (VA), presence of pain, segmental enhancement, and total enhanced segments of the anterior visual pathways. At the last follow-up, immunosuppressive drugs were used more often in the AQP4-IgG + ON group (43.7% vs 74.4%, MOG-IgG + ON vs AQP4-IgG + ON, respectively; p < 0.027). Remarkably better final VA was achieved in MOG-IgG + ON-affected eyes (median: 0.0 vs 0.4 logMAR, MOG-IgG + ON- vs AQP4-IgG + ON-affected eyes, respectively; p < 0.001). CONCLUSION: Compared with AQP4-IgG + ON, MOG-IgG + ON tended to present with bilaterality and optic disc edema and demonstrated better visual outcomes.

Prognostic Factors for Visual Outcomes Following the First Episode of NMOSD-Related Optic Neuritis in Affected Eyes.

OBJECTIVE: We aim to identify prognostic factors for visual outcomes following a first episode of neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) in affected eyes. MATERIALS AND METHODS: This was a single-center, retrospective study. The study included 50 individuals who were diagnosed with NMOSD-ON (63 affected eyes) in a tertiary institution over a 12-year period. Data regarding any second, or higher, episodes of NMOSD-ON in each eye were not taken into consideration. Medical records of included individuals were reviewed. Demographic data, clinical and magnetic resonance imaging characteristics, and treatment outcomes were collected. Main outcome measures of the study were prognostic factors for good visual outcome (best-corrected visual acuity (BCVA) ≥ 20/200) following an initial episode of NMOSD-ON in affected eyes. RESULTS: Sixty-three affected eyes of 50 individuals (3 men and 47 women) were included. BCVA at nadir that was better than counting fingers (CF) (odds ratio 10.43, 95% confidence interval 1.04, 104.45, p = 0.046) and time from NMOSD-ON onset to intravenous methylprednisolone (IVMP), less than 21 days (odds ratio 10.73, 95% confidence interval 1.91, 60.01, p = 0.007), were significantly associated with good visual outcomes. CONCLUSION: BCVA at nadir that was better than CF and treatment with IVMP within 21 days of symptom onset were important prognostic factors of good visual outcomes following a first episode of NMOSD-ON in affected eyes.

Congenital myasthenic syndromes in the Thai population: Clinical findings and novel mutations.

Congenital myasthenic syndromes (CMS) comprise a heterogeneous group of genetic disorders of the neuromuscular junction. Next generation sequencing has been increasingly used for molecular diagnosis in CMS patients. This study aimed to identify the disease-causing variants in Thai patients. We recruited patients with a diagnosis of CMS based on clinical and electrophysiologic findings, and whole exome sequencing was performed. Thirteen patients aged from 2 to 54 years (median: 8 years) from 12 families were enrolled. Variants were identified in 9 of 13 patients (69%). Five novel variants and two previously reported variant were found in the COLQ, RAPSN and CHRND gene. The previously reported c.393+1G>A splice site variant in the COLQ gene was found in a majority of patients. Five patients harbor the homozygous splice site c.393+1G>A variant, and two patients carry compound heterozygous c.393+1G>A, c.718-1G>T, and c.393+1G>A, c.865G>T (p.Gly289Ter) variants. The novel variants were also found in RAPSN (p.Cys251del, p.Arg282Cys) and CHRND (p.Met481del). Molecular diagnosis in CMS patients can guide treatment decisions and may be life changing, especially in patients with COLQ mutations.

Carboplatin-based regimen in pediatric intracranial germ-cell tumors (IC-GCTs): effectiveness and ototoxicity.

BACKGROUND: Induction chemotherapy with carboplatin followed by radiotherapy has been used for many years for treating intracranial germ-cell tumors (IC-GCTs) in Thailand. The objective of this study was to assess treatment outcomes, focusing on survival and ototoxicity. METHODS: The outcomes of all patients with IC-GCT treated at Ramathibodi Hospital and the Prasat Neurological Institute between 2000 and 2017 were reviewed and analyzed, including all patient characteristics and treatment modalities. Five-year overall survival (OS) and event-free survival (EFS) were analyzed using the Kaplan-Meier method, and factors affecting survival were compared using the log-rank test. RESULTS: Fifty-three patients age 1-14 years (median, 11 years) were included in this study. The median follow-up time was 63 months. The 5-year EFS and OS rates were 94.3% and 96.2% for all patients, respectively. No statistical difference in OS or EFS was observed between the data of recipients in the carboplatin-based and historical cisplatin-based therapies in our institutes. Concerning radiotherapy, omission of radiotherapy or focal irradiation results in worse long-term survival outcomes, but reduction in dose of radiotherapy to less than 40 Gy did not cause any negative impact on survival rates. Furthermore, carboplatin was associated with lower rates of hearing loss than cisplatin (5.7% vs 87.5%). CONCLUSIONS: Induction chemotherapy with carboplatin-based regimens was associated with excellent survival rates and low ototoxicity in patients with IC-GCT. Radiotherapy should be given to all patients with a minimal volume equivalent to whole-ventricular radiotherapy, during which doses of lower than 40 Gy can be effectively used.