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Yotin Chinvarun,1 Chin-Wei Huang,2 Ye Wu,3 Hsiu-Fen Lee,4 Surachai Likasitwattanakul,5 Jing Ding,6 Takamichi Yamamoto7 1Department of Neurology, Phramongkutklao Royal Army Hospital and Medical College, Bangkok, Thailand; 2Department of Neurology, National Cheng Kung University Hospital College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Pediatrics, Peking University First Hospital, Beijing, People’s Republic of China; 4Division of Pediatric Neurology, Children’s Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan; 5Division of Neurology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 6Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 7Department of Neurosurgery, Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital, Hamamatsu, JapanCorrespondence: Takamichi YamamotoDepartment of Neurosurgery, Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Hamamatsu, Shizuoka, 430-8558, JapanTel +81 53 474 2222Fax +81 53 474 3094Email taka-yamamd@sis.seirei.or.jpAbstract: Perampanel is a once-daily, first-in-class AMPA receptor antagonist approved for the treatment of epilepsy and exhibits broad-spectrum efficacy in a range of seizure types when used as both monotherapy and adjunctive therapy. Clinical studies and real-world evidence have demonstrated the advantages of initiating perampanel at low doses and utilizing a slow titration strategy. Initiating perampanel at an early stage has also been shown to be associated with better patient outcomes. However, the optimal use and place of perampanel in clinical practice has not yet been clearly defined for the Asian patient population. Use of perampanel in clinical practice varies markedly across the Asia region because of variation in knowledge, attitudes, and practice. There is currently no specific guidance on best practices for prescribing perampanel in Asian patients or how to optimize treatment strategies to maximize adherence. A group of epilepsy experts attended a virtual meeting in September 2020 to discuss their experience with using perampanel in the Asian practice setting, including their views regarding appropriate patient populations, optimal starting and maintenance doses, optimal titration regimens, key barriers to adherence, and prevention and management of adverse events. This article summarizes key clinical and real-world evidence for perampanel and consolidates the experts’ opinions on optimization of perampanel prescribing and adherence in real-world practice, providing practical strategies for clinicians to implement to improve outcomes for people with epilepsy in Asia.Keywords: perampanel, epilepsy, real-world experience, Asia

Muscular dystrophies and congenital myopathies are heterogeneous groups of inherited muscular disorders. An accurate diagnosis is challenging due to their complex clinical presentations and genetic heterogeneity. This study aimed to determine the utilisation of exome sequencing (ES) for Thai paediatric patients with muscular disorders. Of 176 paediatric patients suspected of genetic/inherited myopathies, 133 patients received a molecular diagnosis after performing conventional investigations, single gene testing, and gene panels. The remaining 43 patients from 42 families could be classified into three groups: Group 1, MLPA-negative Duchenne muscular dystrophy (DMD) with 9 patients (9/43; 21%), Group 2, other muscular dystrophies (MD) with 18 patients (18/43; 42%) and Group 3, congenital myopathies (CM) with 16 patients (16/43; 37%). All underwent exome sequencing which could identify pathogenic variants in 8/9 (89%), 14/18 (78%), and 8/16 (50%), for each Group, respectively. Overall, the diagnostic yield of ES was 70% (30/43) and 36 pathogenic/likely pathogenic variants in 14 genes were identified. 18 variants have never been previously reported. Molecular diagnoses provided by ES changed management in 22/30 (73%) of the patients. Our study demonstrates the clinical utility and implications of ES in inherited myopathies., (© 2023. The Author(s).)

Background: Juvenile dermatomyositis is a rare condition, but it is the most common idiopathic inflammatory myopathy in pediatric patients., Aim: To study the clinical manifestations, investigations, treatment, clinical course, and outcomes of juvenile dermatomyositis in Thai children., Method: This retrospective study included juvenile dermatomyositis patients treated at Siriraj Hospital, a 2,300-bed national tertiary referral center in Bangkok, Thailand, from 1994 to 2019., Results: Thirty patients (22 females and 8 males) were included with a female to male ratio of 2.7:1. Median age at diagnosis was 5.1 years (range, 2.6-14.8 years). Median duration of illness before diagnosis was 6.5 months (range, 0.3-84.0 months). Acute and subacute onset occurred in the majority of patients. Presenting symptoms included muscle weakness in 27/30 (90%), skin rash in 26/30 (86.7%), muscle pain in 17/26 (65.4%), and arthralgia in 4/18 (22.2%) of patients. Dermatologic examination revealed Gottron's rash, heliotrope rash, and periungual telangiectasia in 25/30 (83.3%), 21/30 (70.0%), and 15/24 (62.5%) of patients, respectively. Interestingly, scalp dermatitis was found in 8/21 (38.1%) of patients. The most commonly used treatment regimen in this series was a combination of prednisolone and methotrexate. During the median follow-up of 3.1 years (range, 0.0-18.5 years), only one-third of patients were seen to have monocyclic disease. Extraskeletal osteosarcoma at a previous lesion of calcinosis cutis was observed in one patient at 12 years after juvenile dermatomyositis onset., Limitations: This was a retrospective single-center study, and our results may not be generalizable to other healthcare settings. Prospective multicenter studies are needed to confirm the findings of this study., Conclusion: juvenile dermatomyositis usually poses a diagnostic and therapeutic challenge, which can be compounded by the ethnic variations in the clinical presentation, as observed in this study. Asian patients tend to present with acute or subacute onset of disease, and arthralgia and/or arthritis are less common than in Caucasian patients. Scalp dermatitis is not uncommon in pediatric juvenile dermatomyositis patients. An association between juvenile dermatomyositis and malignancy, though rare, can occur.

Case series reports on clinical features of pediatric hereditary neuropathy in Thailand is scarce. Subtype and clinical presentation in childhood-onset CMT differ from adult-onset. The aim of this study is to investigate the CMT phenotype in Thai children. We retrospectively reviewed children diagnosed with CMT who followed up with Pediatric Neurology, Siriraj Hospital from January 1999 to June 2016. CMT subtypes determined by clinical presentation and neurophysiologic studies. Mutation analysis of PMP22 genes was performed in all demyelinating cases. The disease burden was assessed by CMT Neuropathy Score version 2 (CMTNSv2), CMT Examination Score (CMTES) and CMT Pediatric Scale (CMTPedS). 30 patients from 29 families with Hereditary Neuropathies, 25 diagnosed with CMT and 5 with HSAN. 8-year-old was the average age at first medical visit with disease-related problems. Twenty (67%) were male. Twenty-three were sporadic (77%). 16.7% was autosomal dominant and 6.7% was autosomal recessive. Clinical presentations in CMT children were walking difficulty and foot deformities. Nine (36%) CMT patients had demyelinating and sixteen (64%) had axonal. Forty percent had a history of delayed walking after 15-month-old. Foot deformities presented in all CMT patients, and twelve had foot surgery. 2 axonal CMT patients were wheelchair-dependence. Mean (SD) CMTNSv2, CMTES and CMTPedS were 15.44(9), 11.05(7) and 34(4) respectively. Our findings suggest Thai CMT children are predominantly axonal type. Patients with low socioeconomic status and mild symptoms may not seek healthcare. International collaboration in genetic testing is crucial in diagnosis and initiation of clinical trials in future., Competing Interests: All authors declare no conflicts of interest.

Background: Duchenne Muscular Dystrophy (DMD) is the most common genetic neuromuscular disorder in children. This chronic illness may impact the physical, family, social and school life of affected children and their families. These impacts can be assessed using a disease-specific measure of health-related quality of life (HRQOL). The Pediatric Quality of Life Inventory™ (PedsQL™) 3.0 DMD Module is designed to assess quality of life in children with DMD. This study aimed to evaluate the reliability and validity of the Thai version of the PedsQL™ 3.0 DMD Module in Thai children aged 5-18 years., Method and Materials: The Thai translation of the PedsQL™ 3.0 Duchenne Muscular Dystrophy Module was performed in accordance with established guidelines using forward-back translation and was approved by the creator of the instrument. The Thai version of the scale was administered to children with DMD and their parents at the neuromuscular clinic at Siriraj Hospital and during the annual DMD Day meeting. Psychometric properties were established, and a re-test was performed within 2-4 weeks., Results: Fifty-six children were enrolled. An acceptable level of internal reliability was achieved, as measured by α > 0.7 (total score: child report α = 0.88, parent report α = 0.92). Test-retest reliability showed good agreement, with the following intraclass correlation coefficients (ICCs) for the total score (calculated using all subscales from the child reports and parent reports): child report ICCs = 0.74 and parent report ICCs = 0.88. The mean total scale score was 66.03 for ambulatory children and 55.87 (P = 0.08) for non-ambulatory children according to child self-reports and 70.01 (ambulatory) and 54.29 (non-ambulatory) (P ≤ 0.01) according to parent proxy reports. The child self-reports were in acceptable agreement with the parent proxy reports for most subscales (ICC range 0.49-0.81)., Conclusions: The PedsQL™ 3.0 DMD Module Thai version is a reliable and valid measure of disease-specific health-related quality of life in Thai children with Duchenne muscular dystrophy.

People of different ethnic or racial backgrounds may experience variations in pharmacokinetic and pharmacodynamic responses to drug therapies. Our post hoc analysis evaluated the efficacy, safety, and tolerability of perampanel in Asian and non-Asian populations with refractory focal seizures with or without focal to bilateral tonic-clonic (FBTC) seizures. This analysis pooled data from 4 randomized, placebo-controlled, phase-3 studies involving patients aged ≥12 years who have focal seizures with or without FBTC seizures. Patients were receiving 2, 4, 8, or 12 mg perampanel (or placebo) by the end of a 6-week titration period and for a further 13 weeks during the maintenance phase. Efficacy endpoints included median percent change in seizure frequency per 28 days, and 50% and seizure-freedom responder rates relative to baseline. The median percent change in seizure frequency per 28 days from baseline was significantly greater than placebo for perampanel 8 and 12 mg (-31.1% and -38.1% change, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (-21.1% [P = 0.0001], -26.3% [P < 0.0001], and -27.7% [P = 0.0001] change, respectively) in the non-Asian population. The 50% responder rate relative to baseline was significantly greater than placebo for perampanel 8 and 12 mg (40.1% and 43.8%, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (29.4% [P = 0.0002], 32.8% [P < 0.0001] and 34.5% [P = 0.0001]), respectively, in the non-Asian population. Seizure-freedom rate among all patients was 4.9%-11.7% for perampanel 2, 4, 8, and 12 mg. The most frequently reported treatment-emergent adverse events (TEAEs) across both populations were dizziness, somnolence, irritability, headache, and fatigue. The most common psychiatric TEAEs were aggression and irritability. Perampanel demonstrated a favorable and similar risk-benefit profile in both Asian and non-Asian populations with refractory focal seizures., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Aim: To assess the clinical trial and real-world data for adjunctive perampanel in adolescents and develop consensus recommendations to guide the use of perampanel in this population in clinical practice., Methods: In May 2015, 15 epilepsy experts attended a Consensus Development Meeting to assess the clinical trial data for perampanel, specific to the adolescent age group (12-17 years) and develop consensus treatment recommendations., Results and Discussion: Analysis of the adolescent subgroup data of three pivotal placebo-controlled, double-blind, phase 3 trials investigating perampanel in patients with ongoing focal epileptic seizures despite receiving one to three antiepileptic drugs found that perampanel 4-12 mg was superior to placebo. The tolerability profile of perampanel was generally acceptable. Adolescent patients receiving long-term treatment with perampanel in an open-label extension study maintained improvements in seizure control compared with baseline, with a favorable risk-benefit profile. A phase 2 study showed that perampanel had no clinically important effects on cognitive function, growth, and development., Conclusion: Perampanel is a welcome addition to the armamentarium of existing antiepileptic drugs as it represents a new approach in the management of epilepsy, with a novel mechanism of action, and the potential to have a considerable impact on the treatment of adolescents with epilepsy.

We evaluated a boy who had multiple Salmonella septicemia, Aspergillus pneumonia and brain abscesses. His nitroblue tetrazolium (NBT) test was reportedly abnormal. The dihydrorhodamine (DHR) flow cytometry assay was compatible with typical X-linked chronic granulomatous disease (X-CGD). CYBB analysis revealed a novel complex mutation atggacg --> ttca in exon 12 (base pairs 1532-1538). As a result, 3 amino acids Tyr 511, Gly 512 and Arg 513 were deleted and replaced by 2 amino acids, Phe and Gln. The DHR and mutation analysis of his mother showed normal DHR pattern and no mutations in exon 12 of CYBB gene. In conclusion, any children with multiple Salmonella and Aspergillus infection should be suspected of CGD. NBT test, DHR assay and gene analysis are helpful toolsto confirm the diagnosis e v en i n the case of de novo mutation.

A 13-year-old boy had a history of severe headache for two weeks. He also had seizures and vomited many times. Neurological examination was normal except for bilateral papilloedema. Sagittal T1-weighted magnetic resonance (MR) images showed loss of the normal flow void in the superior sagittal sinus. There was hyperintensity, which came from subacute thrombosis in the posterior half of the superior sagittal sinus. MR venography confirmed loss of flow signal in the superior sagittal sinus. There was also thrombosis of the right transverse, right sigmoid, and left transverse sinuses, and haemorrhagic infarctions in the right frontal and left parietal regions. A diagnosis of dural sinus thrombosis with cerebral venous infarction was made. CT, MR imaging, MR venography, and CT venography findings are discussed in patients with cerebral venous thrombosis.

Spinal magnetic resonance (MR) imaging of a 3-year-old girl with chronic inflammatory demyelinating polyneuropathy (CIDP) showed thickened and marked enhancement of the lumbosacral nerve roots. These abnormalities resolved after steroid treatment. MR imaging of the cauda equina may be helpful in the diagnosis of CIDP.