The pathogenesis of myasthenia gravis has been largely elucidated over the past half century, and its treatment methods have advanced. There are fewer cases of childhood-onset myasthenia than adult-onset myasthenia; therefore, it is desirable to study the pathogenesis and treatment methods that account for the unique growth and development of children.

  Epidemiological studies conducted by the Ministry of Health, Labor and Welfare have shown that according to the age of onset, the number of Japanese patients with myasthenia gravis in Japan differs from that of Caucasian patients in Europe and the United States; these studies also show that myasthenia gravis is more frequent in early childhood. Recently, myasthenia gravis has been reported globally. The pattern of the number of patients according to the age of onset differs between East Asia and Western Europe, confirming that the pattern in Japan is common to East Asia. Furthermore, there are racial differences in autoimmune myasthenia and congenital myasthenic syndromes, and the pathogenesis and relationship between them are gradually becoming clearer. It has also become clear that there is some variation in the choice of treatment methods depending on the region. In this paper, we will introduce the recent findings in myasthenia gravis, focusing on the differences in its pathogenesis.

  Objective: To clarify the adverse effects of enzyme-inducing antiepileptic drugs (EIAED) on lipid and bone metabolism in pediatric patients. Methods: The subjects were pediatric outpatients aged 1 to 19 years who were diagnosed with epilepsy and were taking antiepileptic drugs. We divided the patients into group E, who received EIAED (carbamazepine, phenytoin, and phenobarbital) and group N, who did not. From medical records, we examined the laboratory test values of total cholesterol (TC), triglycerides (TG), total alkaline phosphatase (ALP), hepatic alkaline phosphatase, and bone-type alkaline phosphatase, and analyzed the relationship between patient background and motor function. Results: The total number of patients was 35, 13 in group E, and 22 in group N, and there was no significant difference in patient background. A comparison of laboratory test values of all subjects between groups E and N showed a significant difference only in TG (130.6±80.0 and 80.0±39.3 mg/dL, respectively; p=0.049). Total ALP and bone-type ALP was significantly higher in group E in children with gross motor function classification system (GMFCS) V (p=0.027 and p=0.034, respectively). Conclusions: EIAED may affect lipid and bone metabolism and requires regular evaluation even in children. As patients with GMFCS V are susceptible to changes in bone metabolism, it is desirable to measure not only ALP values but also bone resorption markers and bone density.

  Objective: To investigate long-term functional outcomes of children with hemimegalencephaly after hemispherotomy to develop appropriate interventions based on adequate goals. Methods: We retrospectively evaluated nine children (2 males and 7 females; age at evaluation 6-18 years) with hemimegalencephaly who had visited Bobath Memorial Hospital from January 2001 to July 2020. Outcomes of epileptic seizures, gross motor function, upper limb function of the affected side, and intellectual development were investigated. Results: All nine children had undergone hemispherotomy. The age at the surgery was between 2 and 42 months (median 6 months), and more than 5 years had passed until the time of investigation. Epileptic seizures had disappeared in seven children and remained in two. Seven of the nine children could walk independently and the age at initial walk was between 3 and 7 years (median age, 4 years). All the children needed orthosis for the affected lower limb, and two had undergone orthopedic surgery for clubfoot. Regarding the function of the affected upper limb, five could grasp and release objects, and four could move the shoulder or elbow with some limitations. Among the eight children consecutively evaluated using the Kyoto Scale of Psychological Development 2001, seven showed moderate or severe intellectual disability (developmental quotient<50) after infancy, but four out of all had gradually developed and attained intellectual ability better than that at late infancy. Conclusions: Children with hemimegalencephaly, in addition to early epilepsy surgery and medication, require physical therapy, orthosis, and orthopedic treatment for achieving independent walking, occupational therapy for better utilization of the affected upper limb, and special educational support for facilitating intellectual development through collaborated multidisciplinary interventions.

  We report a case of intractable epilepsy cured after treatment with methylprednisolone pulse (MP) therapy, despite failure of seizure control by polytherapy and corpus callosotomy. A patient had onset of epileptic spasms at 4 months of age, and was diagnosed with West syndrome at 6 months of age. Initially ACTH therapy controlled seizures transiently, but subsequent relapse did not respond to various AEDs. He was diagnosed with Lennox-Gastaut syndrome at 3 years and 11 months, and underwent corpus callosotomy (anterior two-thirds) at 4 years and 10 months for drop seizures. After initial control, seizures relapsed and he visited our hospital at 7 years and 6 months while being treated with CLB, VPA, ZNS and LTG. After reducing the AEDs, cerebrospinal fluid test showed mild increases in protein and albumin concentrations, and immune-mediated pathophysiology was suspected. We started MP therapy with oral pranlukast, achieving seizure control after two courses of MP therapy. Regular MP therapy was continued until 12 years of age. At age 16 years, freedom from seizure was maintained without any drug. MP therapy can be considered after reducing AEDs (polypharmacy) in patients with intractable epilepsy.

  The neurophysiology of aggravation or improvement of symptoms in dystonia patients due to their mental status remains unclarified. The patient is a DYT11 case (SGCE NM_003919.3 : c. 233-2A>G, de novo mutation) who developed focal dystonia at the age of 5 years. In this case, transcranial magnetic stimulation (TMS) was used during movement to measure the silent period (SP) during the affected side hand contraction and bilateral hands contraction. SP was used as an index of interhemispheric inhibition. SP was also compared in the presence or absence of distraction (mental calculation). In addition, motor related cortical potentials (MRCP) and contingent negative variations (CNV) were measured in order to investigate abnormalities in the movement preparation state. The patient’s SP in TMS was shorter in bilateral hands contraction than in the affected side hand contraction alone, as opposed to controls. SP during bilateral hands contraction was prolonged and recovered with distraction compared to that without distraction. MRCP recordings were not normal and CNV appeared. From the results in this dystonia case, it was believed that the decrease in interhemispheric inhibition was involved in abnormalities during movement, and that abnormalities in movement plan and cognitive overload were involved in abnormalities in movement preparation. It is possible that distraction improved the symptoms by eliminating the decreased interhemispheric inhibition. We consider these data to be valuable by showing some neurophysiological basis of psychological effects in dystonia.

  Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by mutations in the SMN1 gene. Recently, much progress has been made in therapeutic strategies used to treat SMA patients. Onasemnogene abeparvovec (OA), a viral vector-based gene therapy, was approved for clinical use in Japan in 2020. There have been no previous reports on the use of OA in Japan. A case was 14-day-old boy, born at 38 weeks and weighted 2965 g. His sister was SMA type 1. He was referred to our hospital at the age of 14 days, for feeding problems after birth. Since he showed general hypotonia and had a family history of SMA, genetic testing was performed. SMA was diagnosed at the age of 23 days by the detection of homozygous deletions in the SMN1 gene, and OA was administered at 50 days. Transient fever, elevation of liver enzyme and cardiac troponin I was observed. His motor function score, assessed by the scale for infantile SMA (CHOP-INTEND), increased from 11 points at baseline to 30 points at 5.5 months after treatment. The early treatment of OA is thought to be important to maximize efficacy. In our case, it took around one month to initiate OA treatment. The delay was related to testing for indication, drug supplies, and practical arrangement for treatment. For early OA treatment, the establishment of a therapeutic system including cooperation with OA-experienced hospital may be necessary.

  Langerhans cell histiocytosis (LCH) can develop in various organs, and the lesions are distributed systemically. Bone lesions often occur in the petrous apex, which may exhibit laterality as a normal mutation, and differentiating them from tumors is important. Here, we report a case in which LCH was difficult to diagnose because it originated in the petrous apex. The patient was an 8-year-old boy who experienced headache, nausea, and right abductor nerve palsy 2 weeks before admission. Blood tests and head computed tomography (CT) revealed no abnormalities. MRI of the head revealed a lateral difference in the petrous apex, but this was not considered abnormal. As right facial nerve palsy also appeared during follow-up, head CT of bone and contrast-enhanced MRI of the head were also performed. These procedures revealed a tumor with bone destruction and a moderate enhancement effect in the right petrous apex. We diagnosed LCH by biopsy after admission. We suspected a lesion near the petrous apex from the course of abduction nerve palsy and facial nerve palsy, and the bone destruction observed on the head CT of bone and the contrast effect on the tumor by the contrast-enhanced MRI were the deciding factors. We reaffirm that the head CT of bone and the contrast-enhanced MRI are useful in differentiating mass lesions at the petrous apex, as well as to allow accurate knowledge of imaging findings of healthy structures.

  Tolosa-Hunt syndrome (THS) is a disease characterized by posterior orbital pain with ophthalmoplegia due to nonspecific granulomatous inflammatory lesions of the cavernous sinus. The inflammation tends to improve in response to normal doses of steroid treatment. The patient was an 11-year-old girl with symptoms of ipsilateral ophthalmoplegia that appeared following posterior orbital pain on the left side. The International Headache Classification 3rd Edition beta (ICHD-3β) Tolosa-Hunt Syndrome Diagnostic Criteria (2013) was met, and a definitive diagnosis of THS was made. The usual dose of steroid treatment was ineffective, and the duration of pain-related illness was prolonged. Immediately after the start of methylprednisolone pulse therapy, the posterior orbital pain disappeared, and the symptoms of ophthalmoplegia gradually improved. There has been no recurrence during 3 years of follow-up. It was suggested that in THS cases wherein the usual dose of steroid is ineffective, methylprednisolone pulse therapy should be attempted, after excluding other diseases.

  Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder presenting with opsoclonus, myoclonus, and ataxia. Though several autoantibodies have been reported to be involved in OMS, the pathogenetic roles of these autoantibodies remain largely unknown. The prognosis of OMS remains unsatisfactory despite standard immune therapies. Herein, we report the case of an infant with OMS and the presence of anti-glutamate receptor δ2 (GluD2) and anti-N-methyl-D-aspartate receptor (NMDAR) antibodies. Rituximab therapy at an early phase led to good prognosis. This case highlights the pathogenetic role of autoantibodies in OMS and the efficacy of early phase rituximab therapy.