Epilepsy is caused by the excessive excitation of neurons due to alterations in the excitation and inhibition balance caused by various factors. Voltage-gated sodium ion (Na＋) channels are responsible for regulating conduction in neurons and play a major role in the development of epilepsy. The genes that code for voltage-gated Na＋ channels, abnormalities of which have been reported in epilepsy patients, include SCN1A, SCN2A, SCN3A and SCN8A. Pathological variants of SCN1A are seen in genetic forms of epilepsy with febrile seizures plus, and variants of SCN2A are seen in benign (familial) neonatal-infantile epilepsy and relatively mild epilepsy. Meanwhile, pathological variants of all of these genes are observed in severe developmental epileptic encephalopathy. Here, abnormalities of these four genes and their phenotypes are described based on the latest findings.

  Objective: This study aimed to establish the Japanese version of internationally used Cerebral Palsy Quality of Life Questionnaire for Adolescents (CPQOL-Teen) Self Report Questionnaire to evaluate the subjective QOL of adolescents with cerebral palsy (CP) in Japan and to examine its clinical utility. Methods: We translated CPQOL-Teen Self Report Questionnaire into Japanese with the permission of the original authors, and applied it to 57 adolescents with CP and 58 typically developed adolescents (TD). Results: The Japanese version of CPQOL-Teen Self Report Questionnaire showed, both in CP and TD groups, sufficient test-retest reliability and internal consistency, and showed sufficient concurrent validity against J-KIDSCREEN-27 as an external criterion. The domain of ‘Feelings about functioning’ of CPQOL-Teen did not correlate with any domain of J-KIDSCREEN-27 in the CP group, suggesting that it may reflect an aspect of QOL specific to adolescents with CP. Differences were presented in QOL ratings between the CP and TD groups in three of the five domains of CPQOL-Teen. The CP group had lower scores in the domains of ‘Communication & physical health’, ‘School wellbeing,’ and ‘Feelings about functioning’, but there were no differences seen between the groups in the domains of ‘General wellbeing & participation’ and ‘Social wellbeing’. Conclusions: The Japanese version of CPQOL-Teen Self Report Questionnaire proved to be a useful assessment scale to evaluate subjective QOL specific to adolescents with CP and may possibly promote effective and comprehensive interventions for them.

  Objective: To clarify the clinical characteristics and surgical prognosis of medial temporal lobe epilepsy (mTLE) resulting from focal lesions in infants and young children. Methods: We retrospectively reviewed the medical charts of 18 patients with mTLE and an onset under 3 years of age. All subjects underwent focal resection surgery at the National Center of Neurology and Psychiatry hospital between January 2007 and July 2018 and were followed-up for more than a year after surgery. Results: The 18 patients consisted of 7 males and 11 females. The median age of onset, age at surgery, and follow-up period were 16, 37, and 55 months, respectively. Although the most frequent seizure symptom at onset was motion arrest (50%), atypical and poorly localized symptoms were observed, including cyanosis (33%), epileptic spasms (28%), tonic seizures (28%), and apnea (11%). While 50% of the patients showed focal abnormalities following an EEG analysis, 39% showed atypical bilateral abnormalities, and 11% had normal readings. On initial imaging, an absence of lesions was seen in 44% of the patients. Furthermore, an interictal ^99mTc-ECD SPECT showed either hypo or hyperperfusion in 75% of the patients, while a ¹⁸F-FDG PET showed hypometabolism in the lesions of all patients. Tumors, focal cortical dysplasia, and hippocampal sclerosis occurred in 12 (67%), 3 (17%), and 2 (11%) cases, respectively. Finally, seizures disappeared in 78% of the patients after surgery. A lack of relationship was found between the localization of the preoperative EEG and the seizure prognosis. Conclusions: Although symptoms and EEG findings may be poorly localized in cases of mTLE in infants and young children, resection surgery can successfully improve patient outcomes. Moreover, performing imaging at regular intervals is helpful for the detection of lesions.

  Objective: To promote a smooth transition from pediatric to adult care for patients with childhood-onset dystrophinopathies, the statuses of transition and collaboration with community-based pediatric facilities among specialized hospitals for neuromuscular diseases were examined. Methods: A mail questionnaire survey was conducted for 29 hospitals, specializing in neuromuscular diseases. Results: Responses were obtained from 24 hospitals, only half of which performed smooth transition pediatric to adult care. 19 of the 24 hospitals replied that smooth transitions were not performed, which suggested existence of difficulties in department-transitions of medical care for childhood-onset dystrophinopathies, with several challenges including the establishment of favorable relationships with patients/families, sufficient information transmission, and determination of appropriate timings for transition. Seven hospitals adopted various approaches to address these issues. The specialized hospitals considered the pediatric services provided by community-based pediatric facilities as problematic in informing the pathophysiology, the condition, and the genetic information to the patients, and in the approach for rehabilitation. As for collaboration with these facilities, many hospitals answered “In addition to community-based pediatric facilities, we, specialized hospitals, also follow the patients”, while defining their role as “providing specialized advice and information”. Conclusions: Patients with childhood-onset dystrophinopathy were followed-up at the local pediatrics during the childhood, but at the specialty hospital after adulthood. Several challenges related to transitions of medical care for patients with childhood-onset dystrophinopathies were identified, but early collaboration between specialized hospitals and pediatric facilities may facilitate the provision of comprehensive care required by these patients during childhood, as well as a smooth transition from pediatric to adult care.

  Objective: Early differentiation of Acute encephalopathy with biphasic seizure and late reduced diffusion (AESD) from febrile status epilepticus (FSE) at the time of first seizure would be clinically valuable. In the current study, we examined a scoring system for predicting the onset of AESD immediately after first seizure. Methods: Subjects were patients diagnosed with FSE and AESD during the period from April 2011 to April 2017. Statistical analysis was performed on patients’ background, clinical course, and initial blood and cerebrospinal fluid findings immediately after first seizure. Using the multivariate analysis, we extracted the predictive factors for the onset of AESD, calculated the cutoff value and constructed a scoring system to predict the onset of AESD based on logistic analysis. Results: There were 55 patients in the FSE group and 28 patients in the AESD group. The multivariate analysis revealed four items as the predictive factors ; (1) the age of onset was 18 months or less, (2) the convulsion duration was 30 minutes or more, (3) Cr was 0.3mg/dL or more, and (4) AST was 42IU/L or more. When we used the cutoff values for the onset of AESD evaluated from these factors, sensitivity and specificity were 91.7% and 65.4%, respectively. Conclusions: Immediately after first seizure, by evaluating four items, it is possible to predict the onset of AESD without observing the state of consciousness.

  Objective: Many cases of epilepsy after encephalitis/encephalopathy are intractable, but there are reports that methylprednisolone pulse therapy (pulse therapy) is effective for seizure control. We aimed to evaluate the relation between cerebrospinal fluid (CSF) levels of cytokines before pulse therapy and efficacy of the therapy, to reveal predictive factors for better seizure outcome. Methods: Among patients with epilepsy after encephalitis/encephalopathy treated by pulse therapy in Shizuoka Institute of Epilepsy and Neurological Disorders, we evaluated 15 patients in whom CSF cytokine and chemokine levels were measured by BioPlex before pulse therapy. The regimen of pulse therapy was one course of methylprednisolone (30mg/kg/day for 3 days) per month. We classified patients with seizure reduction rate of 50% or more into effective group, after three MPs. We compared CSF cytokine levels between the effective group and ineffective group. Results: Five of 15 patients (33.3%) were in the effective group. The ineffective group included eight patients with slight decrease of seizure frequency or improvement of seizure characteristics, and seven patients with behavioral and cognitive improvements such as vocabulary. None of the patients treated with pulse therapy showed increased seizure frequency or cognitive and behavioral deterioration. Age at MP and numbers of MPs were not significantly different between effective group and ineffective group. CSF levels of CCL4 in effective group was lower than ineffective group and disease controls, and CSF levels of IL-9, IL-12, and CCL3 in ineffective group were higher than effective group and disease controls. Conclusions: Our study in epilepsy after encephalitis/encephalopathy may suggest effectiveness of pulse therapy in patients with lower levels of CCL4 in CSF, and ineffectiveness in patients with higher levels of IL-9, IL-12, and CCL3.

  Sialorrhea in children with severe motor and intellectual disabilities may result in medical problems such as dermatitis and dehydration ; however, a standard treatment for these complications has not been established. Sialorrhea can be categorized into two types : true sialorrhea and pseudo sialorrhea. The former is derived from increased amounts of saliva, whereas the latter is derived from dysphagia. Here, we report a case in which atropine sulfate and clonidine were successfully administered to a patient who developed serious sialorrhea with paroxysmal sympathetic hyperactivity (PSH). A boy aged 2 years and 5 months developed cerebral palsy caused by hypoxic-ischemic encephalopathy and he had been diagnosed with pseudo sialorrhea. At 10 months of age, he experienced cardiopulmonary arrest caused by dehydration due to severe sialorrhea and poor feeding of enteral nutrition. Hereafter, he also developed sympathetic hyperfunction symptoms such as hyperthermia, tachycardia, muscle hypertonia, and seizure, which exacerbated the sialorrhea. He was diagnosed with true sialorrhea by measuring the amount of saliva. We considered it complicated with PSH after he experienced cardiopulmonary arrest and administration of Roto extract and scopolamine ointment were not effective. Subsequently, continuous intravenous atropine sulfate was administered, and the amount of saliva markedly decreased. However, since the saliva volume was aggravated with PSH, it improved when clonidine was administered. As a result, hospitalization frequency due to dehydration decreased after treatment initiation. Sialorrhea in children with severe motor and intellectual disabilities may be complicated by PSH, suggesting that treatment with atropine sulfate should be effective.

  Brain-lung-thyroid syndrome (BLTS) is a rare disease often associated with movement disorders such as chorea and is characterized by lesions in the brain, lung, and thyroid gland. A 3-year-old boy had ataxic gait and stuttering, but did not have chorea. He had a history of respiratory disorders and congenital hypothyroidism in infancy. BLTS was suspected based on his medical history and medical examination findings, and sequencing of candidate genes for hypothyroidism identified a de novo nonsense mutation c.664G>T in the NKX2-1 gene. Our findings suggest that, when respiratory disorders and congenital hypothyroidism coexist, it is important to suspect BLTS and consider neurological symptoms in addition to chorea.

  Tuberous sclerosis complex (TSC) is a disease characterized by systemic hamartoma. Among brain tumor lesions associated with TSC, subependymal giant cell astrocytoma (SEGA) is a common complication, whereas glioblastoma is rarely reported. A 9-year-old boy was diagnosed with tuberous sclerosis due to the onset of infantile spasms at 5 months of age. Head CT revealed a subcortical nodule accompanied by a calcification in the left frontal lobe. He experienced several episodes of sudden vomiting without trigger for 2 weeks. Head CT showed a neoplastic lesion with hemorrhage in the left frontal lobe. After several hours, frequent vomiting and consciousness disorder were observed. Re-examination of head CT revealed that intratumoral hemorrhage was rapidly exacerbated and intracranial pressure was elevated. Thus, urgent tumor resection was performed, and glioblastoma was diagnosed by pathological examination. Although SEGA is pathologically benign, glioblastoma is highly malignant, exhibits rapid growth, and is generally associated with poor prognosis. In TSC head lesions, the onset of tumors other than SEGA must also be considered, and prompt image evaluation was deemed to be necessary upon the occurrence of symptoms. Clinicians should be aware that neurological symptoms may be difficult to transmit, due to a high rate of complications of intellectual disability or autism spectrum disorder.

  Herein we report the case of a 7-year-old boy with cyclic vomiting syndrome (CVS) successfully treated with judicious management and medication of autism spectrum disorder (ASD) traits. Radical surgery for esophageal atresia (Gross C) was performed during the neonatal period. The patient’s mother and grandmother both had migraines. The cyclic vomiting began when he was 1 year and 4 months of age, and the episodes occurred 1-3 times monthly. Various drug treatments were tested, but were not effective in controlling the vomiting events. The patient was referred to our hospital at the age of 7 years and 4 months for consultation and treatment. We arrived at a diagnosis of ASD due to observable traits including avoidance of eye contact, obsessiveness, and difficulty in communication. Subsequently, we began individual support and medication for ASD traits to alleviate the CVS. The school has begun to support for his behaviors associated with ASD. Consequently, the psychological anxiety regarding school attendance was addressed, allowing the patient to return to school. When prophylactic drug treatment was changed to the combination of risperidone, amitriptin, and sodium valproate, the vomiting attacks discontinued. The patient is now aged 9 years and 3 months, and has experienced no recurrent vomiting episodes in the past 14 months. In conclusion, it is important to consider the possible coexistence of developmental disorders in patients with intractable CVS, and to provide the reasonable accommodation and treatment for optimal outcomes.

  A ketogenic diet is reportedly effective in controlling intractable seizures in the acute phase of AERRPS. However, if patients with AERRPS experience intestinal failure as an adverse effect of antiepileptic drugs and anesthetics, initiating ketogenic diet therapy may become difficult. A 13-year-old male patient was admitted due to fever, focal to bilateral tonic-clonic seizures and disturbance of consciousness on 6 days of illness. Although multiple antiepileptic drugs and intravenous anesthetics, including high-dose phenobarbital, were administered, the frequency of his seizures increased. Acute encephalitis with repetitive refractory partial seizures (AERRPS) was diagnosed based on his clinical course. To reduce the frequency of the seizures, ketogenic diet therapy was begun on day 14 after onset. Intravenous ketogenic diet therapy was administered concurrently with enteral ketogenic diet therapy. After maintaining these dietary regimens concurrently for six days, the intravenous regimen was discontinued when the ketone bodies in the serum reached a satisfactory concentration and the seizure frequency declined. There was no adverse event requiring intervention. Our experience suggested that short-term intravenous ketogenic diet therapy can be performed safely if the liver and pancreatic enzymes and lipid profile are carefully monitored and may provide a treatment option for patients with intestinal failure in the acute phase of AERRPS.

  We examined the usefulness of the self-assessment of school life for children who have difficulty verbalizing their concerns. Eighty-six students were asked to answer their “concerns” about their school life by using open questions and self-assessment of school life. Compared to open questions, there were significantly more children who were able to verbalize their concerns by the self-assessment of school life, and it was considered that the verbalization of concerns was promoted by the quantification process of their own school life.

  We describe the clinical course of a patient with neuromyelitis optica spectrum disorder who showed reconversion (negative to positive) of AQP4-IgG upon clinical relapse after tapering prednisolone. Because of side effects, prednisolone could not be administered as maintenance therapy to prevent recurrence. Combination therapy with tacrolimus maintained the AQP4-IgG negative state while tapering the prednisolone. Prednisolone should be tapered carefully and the addition of an immunosuppressant should be considered.