The pathogenesis of febrile seizures (FS) remains unknown. It is also unclear whether prolonged FS in childhood facilitate mesial temporal lobe epilepsy (MTLE) in adulthood. Previous studies found that various inflammatory mediators play an important role in childhood convulsive disorders. The present review demonstrates the role inflammatory cytokines and high-mobility group box 1 (HMGB1), an important nucleokine, in FS and acquired epilepsy-associated prolonged FS. Experimental hyperthermia-induced seizures (HS) and prolonged HS have been used in animal models to clarify the mechanisms involved in FS and prolonged FS. In the HS rodent model, interleukin (IL)-1β enhanced HS, conversely, IL-1 receptor antagonist, IL-6 and IL-10 suppressed HS. A case-control study of Japanese patients with FS demonstrated that the −511C/T polymorphism of the IL1B gene was associated with development of simple FS. In contrast, the frequencies of the IL10−592C allele and −1082A/−819C/−592C haplotype were significantly decreased in patients with FS. In the prolonged HS model, IL-1β enhanced acquired epilepsy-associated prolonged HS. HMGB1 also enhanced HS and acquired epilepsy-associated prolonged HS with enhancing astrocytosis in the hippocampus and corpus callosum. The activation of IL-1β and HMGB1 signaling activates the N-methyl-D-aspartate (NMDA) receptor pathways in neurons. A long-term decrease in seizure threshold has also been observed, possibly mediated by acquired epilepsy-related prolonged HS. These findings suggest that IL-1β and HMGB1 might contribute to FS pathogenesis, and infantile prolonged FS combined with IL-1β or HMGB1 overproduction could enhance adulthood epileptogenesis, potentially contributing to the development of MTLE.

  Objective: Respiratory care management is necessary for patients with spinal muscular atrophy (SMA), and training regarding respiratory rehabilitation is routinely provided for those patients as well as their caregivers by our hospital. In the present study, we examined the significance of respiratory rehabilitation in SMA type Ⅱ patients by performing sequential evaluations of their respiratory functions. Methods: We retrospectively evaluated sequential changes in vital capacity (VC), cough peak flow (CPF), and maximum insufflation capacity (MIC) in 13 SMA type Ⅱ patients, as well as CPF accompanied with MIC (MIC-CPF) in 8 such patients. Furthermore, we evaluated the rate of change for those parameters in 5 who underwent spinal fusion surgery before and after the operation. Results: The median age at the first evaluation was 6 years (range 3-17 years) and the median observation period was 4 years (2-9 years). VC level was less than 2,000 ml in each patient, while the MIC level exceeded 2,000 ml in only 1. None had a CPF or MIC-CPF level that exceeded 270 L/min, which is needed to promote expectoration, while those exceeded 160 L/min in 2 and 4 patients, respectively. The rate of change after spinal fusion surgery was −10.9% for VC (n=5), −0.25% for MIC (n=5), −7.3% for CPF (n=5), and 14.4% for MIC-CPF (n=4). Conclusions: Respiratory tract clearance is disturbed in SMA type Ⅱ patients due to respiratory function deterioration. To prevent pulmonary complications, it is important to continue respiratory rehabilitation from the early disease stage.

  Objective: For improvement of educational support for patients with Duchenne muscular dystrophy (DMD), we investigated the current state of school life for patients with Duchenne muscular dystrophy (DMD) and related issues. Methods: A multicenter questionnaire survey was given to parents of DMD patients aged 6 to 20 years who were receiving treatment at 7 hospitals in 5 prefectures in Japan. Results: Parents of a total of 115 patients with DMD returned completed questionnaires. Upon admission to elementary school, 60% of the patients were placed in a regular class, while 5% were enrolled in a special needs school. From the fourth year of elementary school, the number of patients who seemed to enjoy school showed a decreasing trend, while those who did not participate in physical education class showed an increasing trend. At around the fifth year, some required a change to a special needs class or special needs school. Upon admission into junior high school, 60% of the patients were enrolled in a special needs school, while 13% remained in a regular school. Concerning collaboration between physicians and school staff, 77% of the parents expected some level of collaboration, whereas 52% of them answered that there was no collaboration. Conclusions: A large number of DMD patients are placed in a regular class to begin elementary school, though difficulties with school life seem to appear from the fourth year. It is important to share information and adjust the educational environment as necessary in consideration of patient need, as well as consultations among parents, teachers, and attending physicians. The level of collaboration between physicians and school staff in regard to education is lower than expected by parents, thus an effective system for collaboration between the medical and educational fields should be constructed.

  The RAS/MAPK syndromes, including Noonan syndrome, Costello syndrome, and cardio-facio-cutaneous (CFC) syndrome, are congenital developmental disorders caused by germline mutations in genes involved in the RAS/MAPK pathway. Neuroblastoma RAS viral oncogene homolog (NRAS) is one of the causative genes for Noonan syndrome. Here, we report a case of an NRAS mutation associated with a phenotype analogous to that of CFC syndrome. A 16-year-old Japanese girl with severe psychomotor developmental delay was born without complications, and was the second child of healthy and nonconsanguineous parents. However, she was hypotonic, had no head control, and had microcephalus. Brain MRI scans showed agenesis of the corpus callosum and hypoplasia of the frontal lobe. Onset of epilepsy occurred at 1 year and 4 months of age. Interictal EEG showed no abnormal findings, but epilepsy was intractable. Sodium valproate and phenobarbital were not effective, and levetiracetam resulted in worsening of seizures. Seizures are currently controlled with phenytoin, phenobarbital, sodium valproate, and nitrazepam. Whole exome sequencing identified a de novo somatic mutation in NM_002524.4 (NRAS) : c.34G>A (p.Gly12Ser). This mutation was confirmed in 7/46 alleles in blood leukocytes, but not in the hair roots or nails.

  This is a report of a CFC-like syndrome associated with an NRAS mutation and provides further evidence supporting the phenotypic diversity of RAS/MAPK syndromes.

  The patient was a boy, born at 33 weeks by emergency Caesarian section due to non-reassuring fetal status. The birth weight was 1,070 g (−3.57 SD). The patient had a number of anomalies, such as upper airway stenosis, micrognathia, pulmonary artery stenosis, and widely spaced eyes. He had a subclinical seizure on day 1 and had suffered from refractory clonic seizures since the age of 2 months. Whole-exome sequencing revealed deletion of 4p (4p16.3-16.2), known as Wolf-Hirschhorn syndrome (WHS), and duplication of 19q (19q13.33-13.43). Partial duplication of 19q and preterm delivery may modify the characteristics of WHS and worsen epileptic seizures, rendering diagnosis of WHS difficult. We suggest all-inclusive gene analysis, especially when the symptoms differ from those expected from the natural course of the syndrome.