Parents'opinions of the changes in their children's epilepsy treatment during the transition from childhood to adulthood.

Objective: Patients with childhood-onset epilepsy often need continued epilepsy treatment into adulthood. We investigated parents' opinions of the changes in their children's epilepsy treatment during the transition from childhood to adulthood using questionnaires and formulated agendas to build the appropriate medical treatment system for epilepsy. Methods: We distributed questionnaires to parents of patients with epilepsy who were 12 to 18 years old. Results: We distributed 176 questionnaires, and analyzed 79 (45%) questionnaires. Most parents (59%) wanted their child to continue treatment for epilepsy in the pediatrics department because of confidence in the current treatment environment. Most parents (73%) were anxious about their child not being treated in the pediatrics department during future epilepsy medical treatments because of concerns about whether a proper handover from the pediatrics department to other departments is possible. No parent was recommended the departmental transition by the primary pediatrician to other courses for future epilepsy treatment, while 19% of par-ents had a sense of incongruity regarding epilepsy treatment at the current pediatrics department. Parents who were anxious about future epilepsy treatments had significantly fewer general-school students than parents without anxiety. In addition, their children had more seizures than children of parents who were not anxious. Furthermore, they wanted their child to continue treatment for epilepsy in the pediatrics department more than the parents without anxiety. Conclusions: Approximately 70% of the parents were anxious about obtaining future epilepsy treatment in clinical departments other than the pediatrics department. To build a satisfactory medical treatment system for patients with epilepsy having different backgrounds and requiring continued treatment in adulthood, it is important to create a cooperating network consisting of pediatricians, neurologists, neurosurgeons, psychiatrists, and epileptologists.

[Effectiveness of a modified parent training of smaller groups and shorter schedules for children with pervasive developmental disorders].

OBJECTIVE: We have previously reported the modified parent training of smaller groups and shorter schedules (PTSS). In this study, we applied PTSS to the mothers of children with pervasive developmental disorder (PDD) and revealed the new evidence for its effectiveness. METHODS: The participants were 30 mothers of children with PDD aged from 4.2 to 9.6 years. The effectiveness of PTSS was assessed with the confidence degree questionnaire (CDQ) and the child behavior checklist (CBCL), before and after each PTSS course. The recorded interviews were qualitatively analyzed using the KJ (Kawakita Jiro) methods. RESULTS: Average CDQ scores were clearly improved as previously reported. In addition, the CBCL total T-score was significantly improved, which was not observed in the previous study. About KJ methods, six factors that change of mothers recognition were identified. CONCLUSIONS: Our findings provides additional evidence for the usefulness of PTSS for children with PDD.

[Cyclophosphamide pulse therapy effective for childhood-onset refractory multiple sclerosis: a case report].

We report a case of a 15-year-old girl with relapsing-remitting multiple sclerosis (MS) who received cyclophosphamide pulse therapy. At the age of 5 years, she displayed symptoms such as headache and unconsciousness after varicella infection as the first episode of MS. She had been treated with methylprednisolone pulse therapy, intravenous immunoglobulin, interferon-beta1b, and azathioprine. However, she had relapsed 12 times by the age of 15 years. At this time, she showed weakness and severe paralysis of her left leg, and even 1 month after methylprednisolone pulse therapy, she still had gait impairment and showed gadolinium-enhanced lesion on brain magnetic resonance imaging. We then started cyclophosphamide pulse therapy (600 mg/m2) once a month for 12 months combined with interferon-beta1a. She had no serious side effects and she could walk again after 4 months on cyclophosphamide treatment. She has been free from relapse for 2 years and 8 months until the present time. Although only a few studies have indicated the efficacy of cyclophosphamide pulse therapy for childhood MS, we consider careful use of cyclophosphamide could be one of the options for refractory childhood MS.

Supporters' experiences of sensory characteristics of children with profound intellectual and multiple disabilities in after-school daycare centres: A qualitative study.

AIM: To examine how supporters working at after-school daycare centres, who are involved in the lives of children with profound intellectual and multiple disabilities in the community, pay attention to the sensory characteristics of these children and provide support. DESIGN: A qualitative descriptive design. METHODS: Data were collected through semi-structured interviews with 20 supporters in after-school daycare centres. Interview transcripts were analysed via qualitative content analysis. RESULTS: The participants' years of involvement in supporting children with profound intellectual and multiple disabilities ranged from 0.5 to 40 years, with an average of 9.8 years. Data were classified into 68 subcategories, 11 categories and three themes: understanding sensory characteristics and devising support, systematic support and challenges supporting the children. Supporters dealt with physical complications and cooperated with other caregivers to understand and respond to children's sensory characteristics. Difficulties dealing with sensory characteristics, challenges due to the supporters' own characteristics and challenges with the facility's infrastructure were identified. The findings could guide sensory characteristics considerations and support systems in after-school daycare facilities for children with profound intellectual and multiple disabilities. Both support content and challenges in supporting these children were identified.

SLC2A1 gene analysis of Japanese patients with glucose transporter 1 deficiency syndrome.

Glucose transporter 1 deficiency syndrome (Glut1-DS) is a congenital metabolic disorder characterized by refractory seizures with early infantile onset, developmental delay, movement disorders and acquired microcephaly. Glut1-DS is caused by heterozygous abnormalities of the SLC2A1 (Glut1) gene, whose product acts to transport glucose into the brain across the blood-brain barrier. We analyzed the SLC2A1 gene in 12 Japanese Glut1-DS patients who were diagnosed by characteristic clinical symptoms and hypoglycorrhachia as follows: all patients had infantile-onset seizures and mild to severe developmental delay, and ataxia was detected in 11 patients. For the 12 patients, we identified seven different mutations (three missense, one nonsense, two frameshift and one splice-site) in exons and exon-intron boundaries of the SLC2A1 gene by direct sequencing, of which six were novel mutations. Of the remaining five patients who had no point mutations and underwent investigation by multiplex ligation-dependent probe amplification, a complex abnormality with deletion and duplication was identified in one patient: this is the first case of such recombination of the SLC2A1 gene. Changes in regulatory sequences in the promoter region or genes other than SLC2A1 might be responsible for onset of Glut1-DS in the other four patients (33%) without SLC2A1 mutation.

Associations Between Quality of Life, Psychosocial Well-being and Health-Related Behaviors Among Adolescents in Chinese, Japanese, Taiwanese, Thai and the Filipino Populations: A Cross-Sectional Survey.

Health-related behaviors during adolescence have lifelong impacts. However, there are unclear areas regarding the associations between health-related quality of life and demographic characteristics, as well as physical and psychosocial indicators. The aim of this study was to examine the associations between quality of life and body weight, sleep outcome, social support by age, and cohabitants, given that income, self-esteem, lifestyle, emotional, social and behavioral problems were taken into account among adolescents in East and Southeast Asia. A cross-sectional survey was conducted in Zhengzhou of China, Hong Kong, Kansai region of Japan, Taipei of Taiwan, Bangkok of Thailand and Manila of the Philippines between 2016 and 2017 among 21,359 urban adolescents aged between 9 and 16. The results showed that adolescents who had better self-esteem and control of emotions and behaviors had much higher level of perceived quality of life. Those who were overweight or obese, sleepy in the daytime, and not living with parents had worse quality of life compared with those who were not. In conclusion, psychosocial well-being should have a higher priority in the promotion of quality of life among Asian adolescents. Nevertheless, further studies are required to explore the differences in perceived quality of life between genders and countries.

Treatment of infantile spasms by pediatric neurologists in Japan.

OBJECTIVE: To clarify changes in clinical practice for infantile spasms, including West syndrome, in Japan over the past two decades. METHODS: We investigated common treatment strategies for infantile spasms among 157 pediatric neurologists from a designated training facility for pediatric neurology and/or a designated training facility for epilepsy in Japan. A questionnaire was used to investigate use of adrenocorticotropic hormone (ACTH) therapy including daily dose, treatment duration, and tapering off period, and preferred first to fifth-line treatment choices. RESULTS: Among 119 responses (75.8%), 107 enabled analysis of ACTH therapy and 112 were used to determine preferred order of first to fifth-line treatments. Over 80% respondents reported an initial ACTH dose of ≤0.0125 mg/kg/day, with a treatment duration of 14 days and various tapering periods. Following an unfavorable response of seizures to ACTH, 80% respondents increased the dose and/or extended treatment duration. The same ACTH therapy regimen was performed for symptomatic and cryptogenic patients at 95 facilities (88.8%). Preferred orders of therapeutic agents were the same for both symptomatic and cryptogenic patients at 64 facilities (57.1%). Over half the respondents selected vitamin B6 or valproate as the first and second-line treatments instead of ACTH therapy, while ACTH therapy was the most frequently selected third-line treatment. CONCLUSIONS: Current ACTH therapy regimens have lower doses and shorter durations than previously reported. However, treatment strategies for infantile spasms have not changed much in two decades. ACTH therapy should be the first/second-line treatment rather than third-line or later, especially for cryptogenic infantile spasms.

[Effect of carbamazepine on epilepsy with 1p36 deletion syndrome].

The 1p36 deletion syndrome is caused by submicroscopic deletion in the subtelomeric region of chromosome 1. Epilepsy is one of the most important features of the syndrome, in addition to the characteristic facial appearance, cardiac anomaly, dysphagia, deafness, mental retardation and growth delay. We identified three patients with this syndrome and assessed the features of complicated epilepsy. In all cases, epilepsy developed during infancy. The seizure types were mainly focal seizure and multiple seizure types including tonic seizure and tonic-clonic seizure. Interictal electroencephalogram showed focal abnormalities. Noticeably, two developed epileptic spasms and hypsarrhythmia in electroencephalogram, just after the administration of carbamazepine (CBZ). Including cases showing epileptic spasms, their epilepsy was easily tractable with anti-epileptic drugs, which could be withdrawn as they aged. All had deleted potassium channel beta subunit (KCNAB2) and gamma-aminobutyric acid A receptor delta (GABRD). CBZ may aggravate various epileptic syndromes, especially, those caused by GABA-A receptor gene mutation. Our cases may suggest the novel correspondence of GABA-A receptor-related epilepsy syndrome and exacerbation of epilepsy triggered by CBZ.

[Clinical efficacy of shortened ACTH therapy --an individualized method for minimization of adverse effects--Part 1. The short-term outcome].

To minimize adverse effects and to get good efficacy of ACTH therapy against West syndrome, we tried a new 2-steps therapeutic protocol consisting of the shortened ACTH therapy and the additional ACTH therapy. In a prospective multi-institutional study, 20 patients with newly diagnosed West syndrome who had failed to respond to high-dose vitamin B6 and zonisamide were treated by this shortened ACTH therapy. Synthetic corticotropin (ACTH-Z 0.025 mg/kg/dose, max 0.25 mg) was administrated intramuscularly seven times on every other day for 14 days. At 1 month after discontinuing corticotropin, spasms and hypsarrhythmia disappeared in 10/20 (50%) and 13/17 (59%) patients respectively. Subsequently, 9 out of the 10 patients with persistent spasms received additional therapy for 1 or 2 weeks with daily intramuscular ACTH-Z, which was tapered off over a few weeks. Including the additional ACTH therapy, the disappearance of spasms and hypsarrhythmia were found in 13 patients (65%) and 13 patients (76%). Adverse effects during the shortened ACTH therapy were fewer than additional ACTH therapy but not statistically significant. Severe adverse effects were not observed in both ACTH therapy. In the 2-steps therapeutic protocol according to the response to ACTH, favorable results were obtained in seizure control, EEG findings and the degree of adverse effects.

Verification of the reliability and validity of a Japanese version of the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-J).

OBJECTIVE: A Japanese version of the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-J) was developed using international guidelines as a QOL scale for childhood epilepsy; its reliability and validity were examined, focusing on Japanese pediatric epilepsy patients applicability. METHODS: A pilot test questionnaire survey was conducted; involving parents of pediatric epilepsy patients aged 4-15 undergoing outpatient treatment. 278 responses were obtained and analyzed. RESULTS: Internal consistency for the 16 QOLCE-J subscales, except for , was sufficient, and a high overall coefficient α was obtained. The intraclass correlation coefficient was also high, supporting the test-retest reliability of this version. Associations among the subscales, high correlations of r>0.7 were observed among , , and , representing cognitive and behavioral aspects, and among these and . In contrast, correlations among others were moderate or weaker. Furthermore, correlations of r>0.35 were observed among the subscales of the SDQ (Strength and Difficulties Questionnaire) used as an external criterion and the QOLCE-J, confirming the criterion validity of the study version. Analysis of associations between the total QOLCE-J score and pathology of epilepsy, found significant correlation with age of onset and frequency of seizures, ADL, and antiepileptics side effects' symptoms. QOLCE has mostly been used in treatment resistant pediatric patients, the influence of interictal period presently observed, like antiepileptic side effects' symptoms; suggest usefulness for pediatric patients with seizures under control. CONCLUSIONS: The QOLCE-J with sufficient reliability and validity may be applicable as a QOL scale for Japanese children with epilepsy.

Prognostic factors for acute encephalopathy with bright tree appearance.

OBJECTIVE: To determine the prognostic factors for encephalopathy with bright tree appearance (BTA) in the acute phase through retrospective case evaluation. METHODS: We recruited 10 children with encephalopathy who presented with BTA and classified them into 2 groups. Six patients with evident regression and severe psychomotor developmental delay after encephalopathy were included in the severe group, while the remaining 4 patients with mild mental retardation were included in the mild group. We retrospectively analyzed their clinical symptoms, laboratory data, and magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) findings. RESULTS: Patients in the severe group developed subsequent complications such as epilepsy and severe motor impairment. Univariate analysis revealed that higher maximum lactate dehydrogenase (LDH) levels (p=0.055) were a weak predictor of poor outcome. Maximum creatinine levels were significantly higher (p<0.05) and minimal platelet counts were significantly lower (p<0.05) in the severe group than in the mild group. Acute renal failure was not observed in any patient throughout the study. MRS of the BTA lesion during the BTA period showed elevated lactate levels in 5 children in the severe group and 1 child in the mild group. MRI performed during the chronic phase revealed severe brain atrophy in all patients in the severe group. CONCLUSIONS: Higher creatinine and LDH levels and lower platelet counts in the acute phase correlated with poor prognosis. Increased lactate levels in the BTA lesion during the BTA period on MRS may predict severe physical and mental disability.

[Survey of vaccination and viral infections for children with severe myoclonic epilepsy in infancy].

A study group for establishment of a proposed immunization program for neurologically high risk children (Chief, Kihei Maekawa) sponsored by the Ministry of Health, Labour and Welfare of Japan is preparing a proposal for patients with epilepsy. Severe myoclonic eplepsy in infancy (SMEI) is an intractable epilepsy which often presents with status epilepticus and triggered by hyperthermia and viral infections. In this study we investigated the history of vaccination in children with SMEI to compare the risk of vaccination with that of natural contraction of infection. Fifty-eight patients with SMEI, aged from 2 to 25 years, were enrolled in this study. A total of 359 vaccines were given to these subjects. The vaccination rates were high for BCG (71%) and polio (1st; 71%, 2nd; 53%), and then fell gradually after the onset of SMEI (DPT-1st; 48%. DPT-2nd; 45%, DPT-3rd; 38%, DPT-4th; 24%, mumps; 21%, varicella; 19%, rubella 31%). However, the measles vaccine was given at a relatively high rate (55%) before the age of three. When patients suffered from measles, rubella, mumps or influenza, they had a high risk of severe neurological complications, such as convulsive status, disturbance of consciousness and encephalopathy. These complications were documented in 63% of all episodes of naturally contracted infections. This rate was significantly higher (p < 0.0001) than that associated with vaccination (7.2%). However, hyperthermia and convulsion developed more frequently (p = 0.012) after measles vaccine was given, as compared to other vaccines. Thus, administration of these vaccines to patients with SMEI in conjunction with other preventive measures against seizure induced by hyperthermia, may meet the needs of their parents.

Development and verification of child observation sheet for 5-year-old children.

The aim of the study was to develop a newly devised child observation sheet (COS-5) as a scoring sheet, based on the Childhood Autism Rating Scale (CARS), for use in the developmental evaluation of 5-year-old children, especially focusing on children with autistic features, and to verify its validity. Seventy-six children were studied. The children were recruited among participants of the Japan Children's Cohort Study, a research program implemented by the Research Institute of Science and Technology for Society (RISTEX) from 2004 to 2009. The developmental evaluation procedure was performed by doctors, clinical psychologists, and public health nurses. The COS-5 was also partly based on the Kyoto Scale of Psychological Development 2001 (Kyoto Scale 2001). Further, the Developmental Disorders Screening Questionnaire for 5-Years-Olds, PDD-Autism Society Japan Rating Scale (PARS), doctor interview questions and neurological examination for 5-year-old children, and the Draw-a-Man Test (DAM) were used as evaluation scales. Eighteen (25.4%) children were rated as Suspected, including Suspected PDD, Suspected ADHD and Suspected MR. The COS-5 was suggested to be valid with favorable reliability (α=0.89) and correlation with other evaluation scales. The COS-5 may be useful, with the following advantages: it can be performed within a shorter time frame; it facilitates the maintenance of observation quality; it facilitates sharing information with other professions; and it is reliable to identify the autistic features of 5-year-old children. In order to verify its wider applications including the screening of infants (18months to 3years old) by adjusting the items of younger age, additional study is needed.

Sleep problems in physically disabled children and burden on caregivers.

AIM: The present study was implemented to investigate relationships between sleep problems in physically disabled children and sleep quality and perceived burden of caregivers. METHODS: Subjects comprised 100 caregivers of disabled children, including 96 mothers, 2 fathers and 2 grandmothers. Questionnaires included demographic data for children and caregivers, sleep problems of children, and sleep quality (Pittsburgh sleep quality index (PSQI)) and perceived burden on caregivers (Japanese version of the Zarit Burden Interview (J-ZBI)). The sleep problems of children were evaluated according to the following five categories: "Problems initiating and maintaining sleep"; "Problems with sleep-related breathing"; "Problems with excessive somnolence"; "Problems with circadian rhythm"; and "Problems with sleep-related movement". RESULTS: The children comprised 66 boys and 34 girls (age range, 1-17 years). Of these, 65 children could not sit up and 35 could. A total of 88 children were found to have one or more categories of sleep problems. The most common sleep problem was "Problems initiating and maintaining sleep" (64.8%), followed by "Problems with sleep-related movement" (59.1%). J-ZBI was significantly higher in caregivers of children with "Problems initiating and maintaining sleep". PSQI scores were significantly higher in caregivers of children with "Problems with sleep-related breathing" and "Problems with circadian rhythm". A significant correlation was identified between perceived J-ZBI and PSQI of the caregiver. CONCLUSIONS: Increased focus on the sleep problems of disabled children is needed, particularly in relation to the sleep quality and perceived burden of caregivers.

Ictal high-frequency oscillations on scalp EEG recordings in symptomatic West syndrome.

OBJECTIVES: High-frequency oscillations (HFOs) on intracranial electroencephalography (EEG) recordings have been reported to be useful to identify the epileptogenic zone in intractable epilepsy. We investigated whether the ictal HFOs on scalp EEG seen during spasms contributed to identification of the epileptogenic zone in symptomatic West syndrome (S-WS). METHODS: In S-WS, ictal scalp EEGs were recorded during a series of spasms. The HFOs associated with spasms were visualized in the temporally expanded EEG traces and subjected to time-frequency analysis. The results on the distribution of HFOs were compared with that of cortical lesions indicated by neuroimaging. RESULTS: In the 4 children examined, HFOs at 80-150 Hz preceded the clinical onsets of spasms. The maximum augmentation of these HFOs was larger than that of HFOs at 20-70 Hz. The regions of the maximum augmentation of HFOs at 80-150 Hz were identical to the lesions detected by neuroimaging. Two patients who underwent dissection of the area including the area with HFOs resulted in Engel class I. CONCLUSION: Ictal HFOs of spasms on scalp EEG showed a strong association with neuroimaging abnormalities presumed to be the epileptogenic zone in S-WS. Ictal HFOs can thus be a useful marker for exploring lesions for epilepsy surgery.

Long-term developmental outcome in patients with West syndrome after epilepsy surgery.

It has been hypothesized that early seizure control may prevent children with intractable epileptic spasms (ES) from developmental regression and may contribute to better developmental outcome. The effectiveness of surgery for ES has been reported. We investigated long-term post-operative outcomes of seizure control and development in patients with symptomatic West syndrome (S-WS) who underwent epilepsy surgery. Six children who underwent surgical intervention for intractable ES were retrospectively investigated. Cortical malformations were observed on pre-operative MRI in all patients, with hemispheric or multilobar involvement in four children and focal lesions in two. Following surgery, we measured motor function, developmental age (DA), language skills, and sociopsychological function for up to 7years (mean, 4.9years). Post-operative seizure outcome was Engel Class I (n=4) or III (n=2). Motor function and DA was increased following surgery in six and five patients, respectively. Two patients started to speak in sentences following focal resection. Autistic features were noted in four of the five examined patients post-operatively. None of the patients showed developmental regression following surgery. Epilepsy surgery for S-WS with ES may result in good seizure control and improvement in motor development. Improvement in cognitive function was modest in this small cohort of children and autistic features were noted post-operatively in a substantial proportion of the children. While seizure control can be obtained by epilepsy surgery, early intervention for sociopsychological comorbidities may be warranted in children with S-WS.

Effectiveness of modified parent training for mothers of children with Pervasive Developmental Disorder on parental confidence and children's behavior.

AIM: This study used parent training (PT), with modifications to smaller groups and shorter schedules (PTSS), for mothers of children with Pervasive Developmental Disorder (PDD). The usefulness of PTSS was evaluated according to the parent's confidence and child's behavior by questionnaire. METHOD: PTSS was used on 14 mothers of 14 children with PDD of preschool to elementary school age, and performed in small groups of 3-4 mothers each. One PTSS course comprised six consecutive sessions and was completed within three months. The sessions consisted mainly of training for parenting skills, understanding the children's inappropriate behaviors, and helping the children adapt to school. The effectiveness of PTSS was assessed by changes in the scores for confidence degree questionnaire for families (CDQ) and the child behavior checklist (CBCL), determined before and after each course. RESULTS: The average CDQ scores increased for 17 of 18 items after completion of the PTSS course in all 14 mothers. The change was statistically significant in five items. Increases in average CDQ scores were also seen in 10 of 18 items assessed in fathers, although none were significant. The CBCL total T-score decreased in 10 of 14 children (71.4%). The remaining four children showed an increased CBCL total T-score. CONCLUSION: These results indicated that PTSS is useful based on changes in the parents' CDQ scores and children's CBCL scores.

A pilot study on the changes in immunity after ACTH therapy in patients with West syndrome.

Adrenocorticotropic hormone (ACTH) has been the first-line drug for the treatment of West syndrome, although the therapy has various adverse effects. ACTH depresses resistance to a variety of bacterial, viral, protozoal, and fungal agents. The timing of the various vaccinations is delayed after ACTH therapy in Japan, because the immune system is believed to be affected for approximately 6 months. However, the duration of the effect of ACTH on the immune system is not known. Therefore, we examined changes in the immunity levels before and after ACTH therapy. We measured white blood cell counts, lymphocyte counts, T/B cell counts, CD4(+) and CD8(+) T cell counts, CD 4/8 ratio, lymphocyte blastoid transformation by PHA or Con-A, and the levels of IgA, IgM, and IgG before, immediately after, and 1, 3, 6, and 12 months after ACTH therapy. The lymphocyte counts and CD4(+) T cell counts were significantly decreased immediately after and at 1 and 3 months after the therapy, and did not return to the previous levels even at 6 months and 12 months after ACTH treatment; however, these levels returned to within normal limits (within the 95% confidence interval). Immunoglobulin levels did not change after the ACTH therapy. Helper T cells were more depressed than cytotoxic T cells after ACTH therapy.