Clinical Characteristics and Treatment of Juvenile Myasthenia Gravis-A Single-Center Experience.

Juvenile myasthenia gravis (MG) is a rare autoimmune neuromuscular disease, often treated with anticholinesterases, corticosteroids, and immunosuppressants. However, optimal treatment durations remain unclear. This study investigated the clinical characteristics and treatment of juvenile MG, including medication duration. The administration period for all drugs, immunosuppressants, and prednisolone at doses greater than 0.35 mg/kg daily was extracted retrospectively from medical records. Nineteen participants (8 boys, 11 girls) aged 8 months to 14 years (median, 2.5 years) at onset were identified. Fourteen patients (73.7%) had ocular MG and five (26.3%) had generalized MG. Drug treatment was conducted in 18 cases; however, 7 patients did not complete the treatment. Among the patients who completed drug treatment, the duration of treatment ranged from 11 to 100 months (median, 47 months). In the six patients treated with continuous administration of prednisolone or immunosuppressants, the treatment duration ranged from 33 to 99 months (median, 56 months). No severe adverse effects requiring hospitalization were reported. The patients treated with prednisolone or immunosuppressants required at least 33 months of treatment. These results will help develop protocols for juvenile MG treatment.

A novel DLG4 variant causes DLG4-related synaptopathy with intellectual regression.

DLG4-related synaptopathy is a neurodevelopmental disorder caused by a DLG4 variant. We identified a novel de novo heterozygous frameshift variant, NM_001321075.3(DLG4):c.554_563del, in a Japanese girl. Intellectual regression without motor delay was observed at 2 years of age, and she was diagnosed with autism spectrum disorder and attention-deficit/hyperactivity disorder. Recognizing the possibility of DLG4-related synaptopathy in patients with intellectual regression is important for ensuring an accurate diagnosis.

A Pediatric Case of COLQ-Related Congenital Myasthenic Syndrome with Marked Fatigue.

Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous inherited disorder that is treatable. Although the disease usually develops at birth or during infancy, some patients develop the disease in the second to third decades of life. Collagen-like tail subunit of asymmetric acetylcholinesterase (COLQ)-related CMS is CMS with mutations in the COLQ, which results in end-plate acetylcholinesterase deficiency. Diagnostic delay is common in patients with later-onset CMS due to slow progression and fluctuating symptoms. Understanding CMS with atypical and unusual presentations is important to treat this condition effectively. Here, we report a case of COLQ-related CMS. A 10-year-old girl presented with only marked fatigue, which was provoked by exercise but improved after 30-60 min of rest. While motor nerve conduction velocity was normal, a compound muscle action potential (CMAP) with four peaks was recorded. Repetitive stimulation of the accessory nerve exhibited a decrease in CMAP amplitude. Genetic tests revealed compound heterozygous mutations in COLQ (c.1196-1_1197delinsTG and c.1354C>T). Treatment with salbutamol improved fatigue but not the electrophysiological markers. Thus, significant fatigue is a hallmark of COLQ-related CMS; early diagnosis is essential for ensuring appropriate treatment.

Early Developmental Signs in Children with Autism Spectrum Disorder: Results from the Japan Environment and Children's Study.

Autism spectrum disorder (ASD) is a developmental disability in early childhood. Early identification and intervention in children with ASD are essential for children and their families. This study aimed to identify the earliest signs of ASD. Using a large cohort including data from 104,062 fetal records in the Japan Environment and Children's Study, we examined the Ages and Stages Questionnaires® (ASQ-3TM) scores of children with and without ASD. The ASQ-3 comprises five domains: communication, gross motor, fine motor, problem solving, and personal-social. The ASQ-3 scores were obtained at ages 6 months, 1 year, and 3 years. There were 64,501 children with available ASQ-3 data. The number of children diagnosed with ASD was 188 (0.29%) at 3 years of age. The highest relative risk (RR) for any domain below the monitoring score at 6 months was in the communication (RR 1.90, 95% CI 1.29-2.78, p = 0.0041), followed by fine motor (RR 1.50, 95% CI 1.28-1.76, p < 0.0001) domain. A low ASQ-3 score in the communication domain at 6 months was related to an ASD diagnosis at 3 years of age. The ASQ-3 score at 6 months can contribute to the early identification of and intervention for ASD.

Views of the General Population on Newborn Screening for Spinal Muscular Atrophy in Japan.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder that results in progressive muscle atrophy and weakness. As new therapies for SMA have been developed, newborn screening for SMA can lead to early diagnosis and treatment. The objective of this study was to gather the general population's view on screening of SMA in newborns in Japan. A questionnaire survey was conducted on two general population groups in Japan. A total of 269 valid responses were obtained. In the general population, about half of the participants had no knowledge about SMA, and more than 90% did not know about new therapies for SMA. Conversely, more than 95% of the general population agreed with screening newborns for SMA because they believed that early diagnosis was important, and treatments were available. This study revealed that the general population in Japan mostly agreed with screening for SMA in newborns even though they did not know much about SMA. Newborn screening for SMA is promising, but it is in very early stages. Therefore, SMA newborn screening should be performed with sufficient preparation and consideration in order to have a positive impact on SMA patients and their families.

Underlying diseases in sporadic presentation of high creatine kinase levels in girls.

BACKGROUND: Persistent creatine kinase (CK) elevation can occur due to various conditions. Identifying the causes of hyperCKemia is crucial for enabling appropriate follow-up and care. Girls with elevated CK levels may be carriers of Duchenne/Becker muscular dystrophy (DMD/BMD), making diagnosis more difficult than that in boys. This study aimed to elucidate the underlying causes of high CK levels in girls. METHODS: Fourteen girls (seven symptomatic, seven asymptomatic) with persistently elevated CK levels but without a family history of muscle diseases were referred to our hospital between April 2014 and August 2018. Muscle biopsy and/or genetic analysis were conducted for diagnoses. RESULTS: Among the symptomatic girls, six (85.7%) had muscular dystrophy (five DMD/BMD carriers, and one sarcoglycanopathy [limb-girdle muscular dystrophy: LGMDR4]), and one had dermatomyositis. Among the asymptomatic girls, four (57.1%) had muscular dystrophy (three DMD/BMD carriers, and one calpainopathy [LGMDR1]), and three were undiagnosed. CONCLUSION: Our results indicate that muscular dystrophy, including DMD/BMD carriers, must be considered in girls with highperCKemia regardless of symptoms presentation, and in symptomatic girls with dermatomyositis. Investigations in girls with hyperCKemia should be performed under proper ethical considerations. Further research is necessary to develop a diagnostic strategy for girls with hyperCKemia.

Emotional and behavioral problems in pediatric patients with migraine and tension-type headache.

OBJECTIVE: This study aimed to investigate the associations between psychopathological characteristics of children and adolescents with primary headache, as measured by the Strengths and Difficulties Questionnaire (SDQ), and treatment outcomes. METHODS: A cohort study was conducted on 124 pediatric patients with primary headache. At the first consultation, the SDQ was completed by the parents. The analysis of treatment efficacy was conducted on 90 patients with a follow-up period of at least one year. Treatment responders were defined as those who showed 50% reduction in the headache frequency. First, an analysis of the SDQ total scores and five subscales, among the migraine and tension-type headache groups, was conducted for 124 participants. Second, the association between the SDQ scores and treatment outcomes in the groups with periods of improvement of less than three months and three months or more were analyzed in 90 patients. RESULTS: Migraine patients displayed more difficulties than strengths in terms of the total score (p = .004) and in the emotional symptoms subscale (p = .012) compared with tension-type headache patients. Migraine patients who required more than three months to show improvement displayed more peer problems (p = .020), while tension-type headache patients who required more than three months to show improvement displayed fewer conduct problems (p = .007). CONCLUSION: Evaluation of patient characteristics using the SDQ at first consultation can predict the treatment outcome. Moreover, it can help provide appropriate initial treatment and improve outcome of primary headache in children.

Transient extreme spindles in a young child with anti-NMDAR encephalitis: A case report.

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a type of immune-mediated encephalitis, which is a new category of treatment-responsive paraneoplastic encephalitis. In patients with this disease, electroencephalography (EEG) shows non-specific findings, but recently, a unique EEG pattern, named the extreme delta brush, was detected in 40% of adult patients and was suggested to be specific to this type of encephalitis. Here, we describe a two-year-old boy with anti-NMDAR encephalitis, who presented with speech arrest and disturbances of gait and cognition several weeks after developing febrile convulsions. In the early stages of the disease, EEG showed 14-16 Hz, continuous, fast waves characterized by a high amplitude (200-500 µV), very diffuse spreading, and a sharp morphology, during light sleep only, which was compatible with extreme spindles. As the patient's symptoms worsened, this finding was replaced by rhythmic, diffuse, high-voltage, slow waves. Immediately after immunomodulatory therapies, including intravenous methylprednisolone and immunoglobulin, his clinical manifestations and EEG abnormalities appeared to improve. We propose that although the extreme spindle is a non-specific finding of this type of encephalitis, early EEG monitoring might be necessary to detect not only the extreme delta brush pattern, but also non-specific findings, including extreme spindles, which would aid early diagnosis and treatment.