An adolescent case of ASXL3-related disorder with delayed onset of feeding difficulty.

BACKGROUND: ASXL3-related disorder, first described in 2013, is a genetic disorder with an autosomal dominant inheritance that is caused by a heterozygous loss-of-function variant in ASXL3. The most characteristic feature is neurodevelopmental delay with consistently limited speech. Feeding difficulty is a main symptom observed in infancy. However, no adolescent case has been reported. CASE PRESENTATION: A 14-year-old girl with ASXL3-related syndrome was referred to our hospital with subacute onset of emotional lability. Limbic encephalitis was ruled out by examination; however, the patient gradually showed a lack of interest in eating, with decreased diet volume. Consequently, she experienced significant weight loss. She experienced no symptoms of bulimia, or food allergy; therefore, avoidant/restrictive food intake disorder (ARFID) was clinically suspected. CONCLUSIONS: We reported the first case of ASXL3-related disorder with adolescent onset of feeding difficulty. ARFID was considered a cause of the feeding difficulty.

The Impact of Simulation-Based Training on Self-Efficacy in Sedation for Pediatric Magnetic Resonance Imaging.

Background: In Japan, approximately 35% of facilities experience sedation-related complications for pediatric magnetic resonance imaging (MRI), including severe complications such as respiratory and cardiac arrests. In the medical education field, simulation improves not only the quality of real emergency response but also health care workers' self-efficacy. Individuals with high self-efficacy are better prepared at handling diverse conditions. However, there is no research examining the impact of sedation simulation for pediatric MRI on the self-efficacy of health care workers. This study aimed to retrospectively investigate the impact of sedation simulation for pediatric MRI on the self-efficacy of health care workers in sedation. Methods: The study was conducted on August 18, 2023, and enrolled pediatricians, nurses, and radiological technologists. The impact of sedation simulation for pediatric MRI on the participants was analyzed using confidence scale scores and part of the Pediatric Resuscitation and Escalation of Care Self-Efficacy Scale (PRSES), before and after sedation simulation for pediatric MRI. Results: Eighteen participants (six pediatricians, six nurses, and six radiological technologists) were included in this study. Regarding confidence scale scores, a significant improvement was observed in the overall group (P = 0.002) and among the nurses (P = 0.0036). Regarding the item 'When confronted with a clinically deteriorating child, I know how to ask for assistance' of PRSES, a significant improvement was observed in the overall group (P = 0.0035) and among the radiological technologists (P = 0.048). Conclusion: There's a potential for sedation simulation for pediatric MRI to increase the self-efficacy of health care workers in MRI sedation. Our findings suggest that this training has a valuable role in preparing health care workers to practice sedation for pediatric MRI.

Impact of clinical clerkship integrated with clinical ladder on attending physicians' teaching self-efficacy.

BACKGROUND: Self-efficacy plays an important role in enhancing the teaching capabilities of attending physicians (APs). The clinical ladder (CL) is an educational approach developed in the field of nursing education that increases difficulty in an incremental manner. However, no previous study has confirmed the effectiveness of CL in medical education. Therefore, this study aimed to examine the effect of clinical clerkship integrated with clinical ladder (CC-CL) on the self-efficacy of APs. METHODS: Sixth-year medical students participated in CC-CL for 6 months starting from April 2023, and the changes in the self-efficacy of APs were retrospectively evaluated. The students were trained by the APs concurrently, and the achievement levels of each student were shared. The primary outcome measure was the physician teaching self-efficacy questionnaire (PTSQ) score. The PTSQ scores before and after CC-CL were analyzed using the Wilcoxon matched-pair signed-rank test. RESULTS: Fifteen APs from the Department of Pediatric and Child Neurology were included in this study. No significant difference was observed in the total PTSQ scores of the APs before and after CC-CL. However, a significant increase was observed in the PTSQ score of APs who participated for at least 2 h per week over a period of more than 3 months (n = 8) after CC-CL (p = 0.022). Furthermore, APs who had received their pediatrician certification < 10 years ago (n = 8) showed a significant increase in the total PTSQ score after CC-CL (p = 0.022). CONCLUSIONS: CC-CL may play an important role in cultivating the self-efficacy of less experienced APs. Further comparative studies must be conducted in the future to validate the findings of this study.

Three Patients of the Early Onset Epileptic Spasms without Hypsarrhythmia.

Epileptic spasms without hypsarrhythmia occur when patients do not display hypsarrhythmia on electroencephalogram (EEG) at the onset and throughout the clinical course. We report three patients of epileptic spasms in patients with early onset, all of whom experienced other types of seizures.We detail three patients (two boys and one girl) of epileptic spasms without hypsarrhythmia, occurring between 1 and 3 months of age, with no abnormalities detected on neurometabolic analysis and brain magnetic resonance imaging. Long-term video-EEG monitoring revealed epileptic spasms with focal onset seizures in two patients, and epileptic spasms followed by generalized tonic-clonic seizures in one patient. Hypsarrhythmia was never observed in repeated EEG examinations. Two patients achieved seizure freedom and improved development through treatment with topiramate alone or in combination with valproate, without requiring hormonal therapies or vigabatrin. The remaining patient achieved seizure freedom following administration of antiseizure medications, including topiramate, after a trial of adrenocorticotropic hormone therapy.We report the cases of three patients with early onset epileptic spasms without hypsarrhythmia. All patients achieved seizure freedom after topiramate treatment. Topiramate may be considered as a relatively effective antiseizure medication for early onset epileptic spasms without hypsarrhythmia.

Febrile seizure in children with COVID-19 during the Omicron variant-predominant era: A single-center study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has significantly impacted medical services worldwide. During the Omicron variant-predominant era, febrile seizure (FS) in patients with COVID-19 increased compared to that in the pre-Omicron variant era. Therefore, this study aimed to demonstrate the clinical characteristics of FS in patients with COVID-19. METHODS: We surveyed patients aged < 16 years who presented with FS to the emergency room of Tottori University Hospital. The patients were divided into two groups: FS patients with COVID-19 (FS with COVID-19 group) and FS patients without COVID-19 (FS without COVID-19 group) as per the results of the respiratory multiplex array test. Patients with positive results for both SARS-CoV-2 and other microorganisms were excluded. We obtained data on the patients' clinical backgrounds, symptoms, seizure duration, type of FS (simple or complex), diagnostic examinations, laboratory test results, and treatment. We compared the data between the FS with and without COVID-19 groups. RESULT: A total of 128 patients with FS met the inclusion criteria. Of these, 18 patients and 110 patients were included in the FS with COVID-19 group and without COVID-19 group, respectively. The late FS onset (>60 months) were significantly more common in the FS with COVID-19 group than that in the FS without COVID-19 group. Moreover, patients in the FS with COVID-19 group had significantly longer seizure durations than those in the FS without COVID-19 group. A diazepam (DZP) suppository was administered to 72% of FS patients with COVID-19 after the first seizure during a febrile episode. CONCLUSION: FS patients with COVID-19 had different distributions of age at onset and seizure duration than those without COVID-19. The use of DZP suppositories was more frequent in FS patients with COVID-19 compared to those without COVID-19.

Prognostic factors for employment outcomes in patients with a history of childhood-onset drug-resistant epilepsy.

Objective: The employment outcomes of childhood-onset drug-resistant epilepsy (DRE) has not been studied enough. The aim of this retrospective cohort study is to investigate the employment outcomes of childhood-onset DRE in June 2022 and identify the risk factors associated with non-employment. Materials and methods: The sample consisted of 65 participants ≥18 years of age with a history of childhood-onset DRE. Fifty participants (77%) were salaried employees and 15 participants (23%) were non-employed. Clinical and psychosocial information were evaluated for calculating the relative risk (RR) of non-employment. Results: Regarding medical factors, lower IQ [RR, 0.645; 95% confidence interval (CI), 0.443-0.938; p = 0.022] was positively associated with employment. In contrast, age at follow-up (RR, 1.046; 95% CI, 1.009-1.085; p = 0.014); number of ASMs at follow-up (RR, 1.517; 95% CI, 1.081-2.129; p = 0.016); use of medications such as phenobarbital (RR, 3.111; 95% CI, 1.383-6.997; p = 0.006), levetiracetam (RR, 2.471; 95% CI, 1.056-5.782; p = 0.037), and topiramate (RR, 3.576; 95% CI, 1.644-7.780; p = 0.001) were negatively associated with employment. Regarding psychosocial factor, initial workplace at employment support facilities (RR, 0.241; 95% CI, 0.113-0.513; p < 0.001) was positively associated with employment. In contrast, complication of psychiatric disorder symptoms (RR, 6.833; 95% CI, 2.141-21.810; p = 0.001) was negatively associated with employment. Regarding educational factor, graduating schools of special needs education (RR, 0.148; 95% CI, 0.061-0.360; p < 0.001) was positively associated with employment. Conclusions: Specific medical, psychosocial, and educational factors may influence the employment outcomes of childhood-onset DRE. Paying attention to ASMs' side effects, adequately preventing the complications of psychiatric disorder symptoms, and providing an environment suitable for each patient condition would promote a fine working status for people with childhood-onset DRE.

Risk Factors of Prehospital Emergency Care for Acute Encephalopathy in Children With Febrile Status Epilepticus.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) often develops in children with febrile status epilepticus (FSE) with neurological sequelae. No study has investigated the associations between prehospital emergency care and AESD onset. METHODS: We retrospectively collected the data of children with FSE (>30 min) treated in Tottori University Hospital. We evaluated the prehospital emergency care information, investigating its association with AESD development. RESULTS: We identified 11 patients with AESD and 44 with FSE. The time from onset to the arrival of the emergency medical services (EMS) (OR: 1.12, P = 0.015) and hospital arrival (OR: 1.07, P = 0.009) was positively associated with AESD development. In contrast, oxygen saturation levels in ambulances (OR: 0.901, P = 0.013) are negatively associated with AESD development. The time from onset to arrival at the hospital was associated with the time from onset to the administration of antiseizure medications (ASMs) (correlation coefficient: 0.857, P < 0.001), which was significantly associated with AESD development (OR: 1.04, P = 0.039). The cutoff values were 17 minutes from onset to the arrival of EMS (OR: 27.2, P = 0.003), 38 minutes to hospital arrival (OR: 5.71, P = 0.020), and 50 minutes of administration of ASMs (OR: 7.11, P = 0.009). CONCLUSIONS: Prolonged time from onset to hospital arrival and hypoxia in ambulances were associated with AESD development. Shortening transport time, improving respiratory management in ambulances, and the early administration of ASMs might play a role in preventing the development of AESD.

Identifying risk factors for adverse events of pyridoxal phosphate in infantile epileptic spasms syndrome.

INTRODUCTION: Infantile epileptic spasms syndrome (IESS) is characterized by epileptic spasms, regardless of hypsarrhythmia on electroencephalogram or neurodevelopmental delay. In Japan, pyridoxal 5'-phosphate (PLP) is often used as the first-line treatment for IESS because it is effective in a certain number of patients. Although several studies have reported serious adverse events following PLP treatment, no study has investigated the risk factors for such occurrences. OBJECTIVE: To investigate adverse events associated with PLP therapy for the treatment of IESS and to identify the associated risk factors. MATERIALS AND METHODS: We retrospectively evaluated adverse events in 59 patients with IESS at Tottori University Hospital between January 1995 and September 2022. We subsequently collected and analyzed their clinical data and analyzed the risk factors associated with each adverse event. The cutoff values and relative risk (RR) were analyzed for items with significant associations with adverse events. RESULTS: Twenty-seven (51.9%) participants experienced adverse events, including vomiting in 16 participants (59.3%), elevated liver enzyme levels in 15 participants (55.6%), and rhabdomyolysis in two participants (3.4%). No significant differences were observed between the non-adverse events group and the overall adverse events group, as well as between the non-adverse events group and the vomiting group, in terms of the factors examined. However, when comparing the non-adverse events group with the group with elevated liver enzyme levels, age at PLP treatment showed a negative correlation, whereas PLP dose showed a positive correlation with elevated liver enzyme levels. The cutoff dose was 40 mg/kg/day (73.3% sensitivity and 60.7% specificity), and the cutoff age was 9 months (100% sensitivity and 40.0% specificity). RRs of doses ≥40 mg/kg/day and age <9 months were 2.6 and 3.6, respectively. CONCLUSIONS: Adverse events of PLP therapy, including vomiting, elevated liver enzymes, and rhabdomyolysis, were observed in approximately half of the participants. Age under 9 months and a dose ≥40 mg/kg/day were identified as risk factors for elevation of liver enzymes on PLP treatment in infants with IESS, with rhabdomyolysis can occur in the younger or higher dose cases.

Prediction model for long-term seizure and developmental outcomes among children with infantile epileptic spasms syndrome.

Introduction: Children with infantile epileptic spasms syndrome (IESS) are likely to experience poor outcomes. Researchers have investigated the factors related to its long-term prognosis; however, none of them developed a predictive model. Objective: This study aimed to clarify the factors that influence the long-term prognosis of seizures and their development and to create a prediction model for IESS. Materials and methods: We conducted a retrospective cohort study enrolling participants diagnosed with IESS at the Tottori University Hospital. We examined the seizure and developmental status at 3 and 7 years after the IESS onset and divided the participants into favorable and poor outcome groups. Subsequently, we analyzed the factors associated with the poor outcome group and developed a prediction model at 3 years by setting cutoff values using the receiver operating characteristic curve. Results: Data were obtained from 44 patients with IESS (19 female patients and 25 male patients). Three years after epileptic spasms (ES) onset, seizure and development were the poor outcomes in 15 (34.9%) and 27 (61.4%) patients, respectively. The persistence of ES or tonic seizures (TS) after 90 days of onset, moderate or severe magnetic resonance imaging abnormalities, and developmental delay before IESS onset were significantly associated with poor outcomes. Seven years after the onset of ES, seizures and development were the poor outcomes in 9 (45.0%) and 13 (72.2%) patients, respectively. We found that no factor was significantly associated with poor seizure outcomes, and only developmental delay before IESS onset was significantly associated with poor developmental outcomes. Our prediction model demonstrated 86.7% sensitivity and 64.3% specificity for predicting poor seizure outcomes and 88.9% sensitivity and 100% specificity for predicting poor developmental outcomes. Conclusion: Our prediction model may be useful for predicting the long-term prognosis of seizures and their development after 3 years. Understanding the long-term prognosis during the initial treatment may facilitate the selection of appropriate treatment.

A pediatric case of autoimmune encephalitis with chronologically moving seizure foci and cortical lesions: A case report.

INTRODUCTION: Autoimmune encephalitis (AIE) is a relatively newly described category of immune-mediated diseases involving the central nervous system with a wide spectrum of clinical presentations, ranging from relatively mild or insidious onset of cognitive impairment to more complex forms of encephalopathy with medically refractory seizures. Single or multifocal seizures accompanied by neuropsychiatric symptoms and cognitive or memory impairments are suggestive of clinical features at AIE onset. CASE REPORT: A six-year-old boy presented with repetitive focal seizures, slowly progressive emotional liability, and attention-deficit/hyperactivity disorder-like symptoms. Seizure types varied during the clinical course, sometimes emerging as clusters or statuses. MRI performed during seizure clustering/status revealed moving signal abnormalities. We successfully treated the patient with high-dose intravenous methylprednisolone. Cerebrospinal fluid analysis revealed pleocytosis and marked elevation of antibodies against N-terminals of N-methyl-d-aspartate type glutamate receptor subunits and granzyme B. CONCLUSION: We report a case of moving seizure foci with abnormal MRI findings. Although the onset of psychiatric symptoms slowly progressed to those atypical for AIE, responsiveness to immunotherapy, cerebrospinal fluid pleocytosis, and autoantibodies all indicated AIE. We thus suggest that moving seizure foci and abnormal MRI signals may be findings of AIE.

Possible molecular mechanism for acute encephalopathy by angel-wing mushroom ingestion - Involvement of three constituents in onset.

In Japan in 2004, 59 people who had consumed angel-wing mushroom, Pleurocybella porrigens, experienced acute encephalopathy, and of these 17 died. We purified a lethal protein to mice, pleurocybelline (PC), from P. porrigens. Although PC caused no damage to the brain, PC formed a complex with a lectin (PPL) and showed exo-protease activity, degrading substrates from both N- and C-termini. In addition, the presence of an unstable toxic compound, pleurocybellaziridine (PA), in the mushroom was demonstrated. We hypothesized that the complex and PA are involved in disease development and verified that apoptotic cells in the hippocampus were significantly increased by injection of the mixture of PC, PPL, and PA, indicating that these substances might be involved in acute encephalopathy.

Successful perioperative preparation of a child with autism spectrum disorder in collaboration with his school for special needs education: a case report.

Introduction: The incidence of autism spectrum disorder (ASD) in children is greater than 1%. Children with ASD show an increased rate of hospital contact for several reasons. Perioperative preparation for children with ASD can be challenging; therefore, obtaining information from patients' families prior to surgery is important. However, no previous reports have described the collection of information from educational facilities. Case report: A 12 years-old male patient with ASD was referred for surgery for traumatic dislocation of the left knee joint. Before admission, we obtained valuable information from his parents regarding expected behavioral problems and coping strategies during hospitalization and from his teachers at his school for special needs education. In particular, the information obtained from teachers was specific and practical. Consequently, we could effectively conduct perioperative management based on his specific autistic characteristics. Conclusion: We report a pediatric case of ASD in which favorable perioperative management was successfully achieved by collecting information before admission from family members as well as teachers at the patient's school for special needs education. This management may help in future hospital admissions for children with autism.

A case of ALG11-congenital disorders of glycosylation diagnosed by post-mortem whole exome sequencing.

INTRODUCTION: Congenital disorders of glycosylation (CDG) are inherited inborn errors of metabolism due to abnormal protein and lipid glycosylation that present with multi-systemic manifestations. The heterogeneity of CDG poses a serious diagnostic challenge; therefore, whole-exome sequencing (WES), which plays an increasingly important role in the molecular diagnosis of CDG, is used for examining patients with CDG. CASE REPORT: We report the case of a two-month-old male patient who developed developmental and epileptic encephalopathy (DEE) with intractable seizures and microcephaly. EEG demonstrated a suppression-burst (S-B) pattern, and MRI showed delayed myelination and progressive atrophic changes. Although CDG was clinically suspected, serum transferrin isoelectric focusing analysis appeared to be normal. The patient died by six years of age. Postmortem WES performed approximately 20 years after the patient's death revealed homozygous variants in ALG11 (NM_001004127.3: c.935A > C, p.Glu312Ala), and the patient was diagnosed with ALG11-CDG. CONCLUSION: We present a case of the patient with ALG11-CDG diagnosed using post-mortem WES. The EEG revealed a S-B pattern that indicated severely drug-resistant DEE, which was associated with poor prognosis. If a CDG is suspected, WES should be considered.

Power and connectivity changes on electroencephalogram in postoperative cerebellar mutism.

INTRODUCTION: Cerebellar mutism syndrome is a debilitating postoperative neurological complication following posterior fossa surgery in children. It is characterized by a significant lack or loss of speech. Injury to the dentato-thalamo-cortical pathway is thought to be the main anatomical substrate of cerebellar mutism syndrome; however, few studies have investigated the physiological changes using computed electroencephalogram. CASE REPORT: Herein, we report a case of a nine-year-old girl who developed cerebellar mutism syndrome after excision of an ependymoma of the fourth ventricle and was followed up with evaluation of aphasia, gross motor function, and scalp electroencephalograms. Her language, dysmetria and gait ataxia gradually improved until day 605 after onset. Computed electroencephalogram analyses were performed for the relative power spectrum and connectivity at each frequency band. On the three electroencephalograms at days 109, 299, and 605 after onset, the relative power spectrum at the delta band transiently decreased and then increased, and the relative power spectrums at theta, beta, and gamma bands transiently increased and then decreased. Only the relative power spectrum in the alpha band continuously increased in the occipital area. Additionally, brain connectivity in the delta, beta, and gamma bands increased continuously. CONCLUSION: We report a case of cerebellar mutism syndrome with recovery of language, dysmetria and gait ataxia in 20 months. Electroencephalogram analyses indicated transient changes in the powers of brain activity and continuous improvements in connectivity during the long follow-up, reflecting the plasticity and remodeling of brain function after cerebellar mutism syndrome. Power and connectivity analyses for EEG might be a tool to investigate underlying pathophysiology of cerebellar mutism syndrome.

An Integrated Pulsation-Free, Backflow-Free Micropump Using the Analog Waveform-Driven Braille Actuator.

The widespread adoption of long-term organs-on-a-chip culture necessitates both active perfusions that mimic physiological flow conditions and minimization of the complexity of microfluidic system and fluid handling. In particular, flow in microtissue such as microvascular is free of pulsation and backflow. The refreshable Braille actuator-based integrated microfluidic system can be employed with simple microchannels and setups. However, due to high pulsatile flow and backflow, ordinary Braille-driven micropumps generate non-physiological flow conditions. We have described a simple method for creating steady flow employing Braille actuators driven with a high-voltage analog waveform, called "constant flow waveform", without incorporating complicated structures into the microchannel or actuator. We determined the constant flow waveform by measuring volume change of microchannel caused by actuated Braille pins using a conventional fluorescent dye and microscope. Using the constant flow waveform, we demonstrated that a Braille-driven pump reduced pulsating flow by 79% and backflow by 63% compared to conventional Braille-driven pump. Furthermore, we demonstrated that a parallel pair of three-stranded pin pumps effectively eliminated backflow by driving two pumps with the constant flow waveform half-cycle shifted to each other. Moreover, by raising the driving frequency, we could increase the average flow rate to ~2× higher than previously reported flow rate of a typical Braille-driven micropump.

Thermally Tunable Structural Coloration of Water/Surfactant/Oil Emulsions.

Stimuli-responsive structural color in nature has fascinated scientists, directing them to develop artificial coloration materials that adjust colors in response to external stimuli. Many stimuli-responsive structural color materials have been realized. However, only a few have reported on all-liquid-type materials, which have a particularly desirable feature because they impart their function to the device of any shape. We have previously reported the development of a consistent structural color within a narrow temperature range for all-liquid-type emulsions comprising a long-chain amidoamine derivative (C18AA) and tetraoctylammonium bromide (TOAB). In the present study, we demonstrate that introducing NaCl as an electrolyte affords a highly thermo-sensitive color-changing ability to the emulsions. The structural color of the emulsions can be controlled from red to blue by tuning the temperature. Furthermore, the C18AA and TOAB concentrations can independently regulate the color and coloring-temperature, respectively, realizing that the desired color can develop at a given temperature.

Successful recovery from severe hypertension in a patient with Leigh syndrome.

Hypertension is a rare complication of Leigh Syndrome (LS), but prognosis of patients with hypertension is poor and its presence is indicative of the terminal stage of the disease. Herein, we report a four-year-old girl case diagnosed with LS at 15 months of age who subsequently developed severe hypertension and respiratory failure. Physical examination and laboratory findings did not indicate a secondary cause of hypertension. Her respiratory failure was treated with non-invasive ventilation and hypertension controlled with enalapril, furosemide and spironolactone. To our knowledge, this is the first case of a patient with LS recovering from severe hypertension.

Fast computer hologram generation by flexible-ratio adaptive point-spread spherical wave synthesis.

We propose a flexible-ratio adaptive point-spread spherical wave synthesis method for fast computer-generated hologram calculation. The conventional adaptive point-spread algorithm uses a fixed ratio between the major and minor axes of the point source, whereas the proposed method uses flexible-ratio sources, i.e., ellipses, for more effective calculation. Numerical simulation was conducted to validate the proposed method. The results show that the proposed method has the potential to achieve faster calculation, compared to the calculation in conventional methods, without significant image degradation.

Nevoid basal cell carcinoma syndrome caused by splicing mutations in the PTCH1 gene.

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis such as medulloblastomas and basal cell carcinomas, caused by mutations of the patched-1 (PTCH1) gene. To date, we have detected 73 mutations in PTCH1 and ten of them (14 %) were suspected splicing mutations. Eight out of the ten mutations were localized near the splice donor site. Five mutations were localized within the invariant GT-AG splice site, whereas the other five mutations occurred outside the invariant GT-AG site including the last exonic nucleotide. When the transcripts were examined, all mutations resulted in aberrant splicing, including exon skipping or the activation of cryptic splice sites. This is the first extensive report of NBCCS focusing on splice site mutations, and it highlights the importance of analyzing transcripts especially for mutations lying outside the GT-AG splicing consensus site. In addition, the splice site score calculated by Splice-Site Analyzer Tool provided by Tel Aviv University helped predict aberrant splice patterns in most of the cases.