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.

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.

Clinical characteristics of SARS-CoV-2-associated encephalopathy in children: Nationwide epidemiological study.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sometimes triggers acute encephalopathy as a serious neurological complication in children. We previously reported the clinico-radiological findings of SARS-CoV-2-associated encephalopathy. The advent of the SARS-CoV-2 omicron variant led to a marked increase in pediatric patients with coronavirus disease 2019 (COVID-19); however, epidemiological changes with acute encephalopathy according to the emergence of SARS-CoV-2 have not yet been documented. Therefore, the present study investigated epidemiological differences in SARS-CoV-2-associated encephalopathy during the BA.1/BA.2 and BA.5 predominant periods and also between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. METHODS: We conducted a nationwide survey of SARS-CoV-2-associated encephalopathy in Japanese children between June and November 2022. We compared the present results during the BA.5 predominant period and previous findings during the BA.1/BA.2 predominant period. We also compared the clinico-radiological syndromes of encephalopathy between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. RESULTS: Although many patients with SARS-CoV-2-associated encephalopathy in the BA.5 predominant period had seizures as their initial symptoms, no significant differences were observed in the clinical features. Patients with SARS-CoV-2-associated encephalopathy had worse outcomes than those with non-SARS-CoV-2-associated encephalopathy (p-value = 0.003). Among 103 patients with SARS-CoV-2-associated encephalopathy, 14 (13.6%) had severe types of acute encephalopathy, namely, encephalopathy with acute fulminant cerebral edema (AFCE) and hemorrhagic shock and encephalopathy syndrome (HSES). Also, 28 (27.2%) patients with SARS-CoV-2-associated encephalopathy had poor outcome: severe neurological sequelae or death. Ninety-five patients (92.2%) were not vaccinated against SARS-CoV-2. CONCLUSIONS: In SARS-CoV-2-associated encephalopathy, high percentages of AFCE and HSES can result in poor outcomes.

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.

Mastocytosis in a Case of Noonan Syndrome Caused by a De Novo Pathogenic CBL Variant.

Noonan syndrome is an autosomal dominant disease characterized by multi-organ disorders caused by variants of genes involved in the RAS/MAPK signaling pathway. The nine causative genes including PTPN11 and CBL have been identified. Mastocytosis is a disease characterized by mast cell proliferation in skin, bone marrow, and other organs. To date, no previous cases of Noonan syndrome with mastocytosis caused by a pathogenic CBL variant have been reported. A boy was diagnosed with Noonan syndrome at 8 months of age with facial features and minor anomaly of his body. He presented with brown nodules of 5-10 mm on his body since the age of 2 months. The patient was diagnosed with mastocytosis by a biopsy specimen from brown nodules, which showed infiltration of mast cells. Whole-exome sequencing of the parent-patient trio revealed a de novo pathogenic CBL variant. The occurrence of mastocytosis may be a cue for the analysis of the CBL gene in Noonan syndrome. The CBL gene is involved in mastocytosis and various cancers. In the case of the pathogenic variant, long-term follow-up for the risk of cancers related to the CBL variant is necessary.

Restricted Diffusion in the Bilateral Subcortical Motor Areas Associated with Status Epilepticus in an Infant with Kawasaki Disease.

Status epilepticus (SE) often causes neuronal death in the cerebrum and consequent long-term sequelae. Acute encephalopathy with biphasic seizures and late reduced diffusion is clinically characterized by SE associated with fever and seizure clusters that occur 3-9 days after symptom onset. MRI reveals reduced diffusion in the frontal or frontoparietal subcortical white matter, with sparing of the perirolandic region following seizure clusters. Kawasaki disease (KD) is an acute self-limited vasculitis secondary to activation of the immune system; KD is rarely complicated by acute encephalopathy. We report the case of a male infant who developed SE associated with KD and showed late reduced diffusion in the subcortical white matter beneath the bilateral motor cortices (primary motor, premotor and supplementary motor areas) and the right frontal cortex. The patient had characteristic neurological sequelae in the chronic phase, including clumsiness of fingers and forearms, impaired discrimination of tactile sensation and position sense on digits in his hands and feet, corresponding to the lesions with reduced diffusion at the acute phase.

Natural history of Becker muscular dystrophy: a multicenter study of 225 patients.

OBJECTIVE: Becker muscular dystrophy (BMD) is a milder variant of Duchenne muscular dystrophy (DMD), a lethal X-linked muscular disorder. Here, we aim to investigat the clinical involvement of skeletal, respiratory, cardiac, and central nervous systems in patients with BMD, as well as genotype-phenotype relationships. METHODS: This nationwide cohort study investigated the clinical manifestations and genotype-phenotype relationships in 225 patients with BMD having in-frame deletion from 22 medical centers. The primary outcome was to elucidate the association of genotype with skeletal muscle, respiratory, cardiac, and central nervous system disorders. Descriptive statistics were used to analyze the data. RESULTS: The average age of the subjects was 31.5 (range, 1-81) years. Initial symptoms of BMD were muscular (60%), followed by asymptomatic hypercreatine kinasemia (32.4%) and central nervous system disorders (5.3%). Gait disturbance was observed in 53.8% of patients and the average age at wheelchair introduction was 36.5 years. The ventilator introduction rate was 6.7% at an average age of 36.6 years. More than 30% of patients had an abnormal electrocardiogram and approximately 15% had heart failure symptoms. Cardiac function on echocardiography varied significantly among the patients. The frequencies of seizures and intellectual/developmental disability were 8.0% and 16.9%, respectively. Exon 45-47deletion (del) was the most common (22.6%), followed by exon 45-48del (13.1%). Patients with exon 45-49del patients demonstrated severe skeletal muscle damage. Patients with exon 45-47del and exon 45-55del patients did not require ventilator use. INTERPRETATION: The study provides important prognostic information for patients and clinicians to establish therapy plans and to implement preventative medicine.

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.

Severe pediatric acute encephalopathy syndromes related to SARS-CoV-2.

Background and objectives: To clarify whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cause acute encephalopathy in children and which are the most common syndromes that cause them and what are the outcomes. Methods: A nationwide web-based survey among all members of the Japanese Society of Child Neurology to identify pediatric patients aged < 18 years who developed acute encephalopathy in Japan between 1 January 2020 and 31 May 2022 associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction or antigen tests using pharyngeal swabs. Acute encephalopathy was defined as acute onset of impaired consciousness lasting > 24 h or an altered mental state; neurological symptoms arising within 2 weeks of onset of COVID-19 or multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome (PIMS); evidence of SARS-CoV-2 infection; and reasonable exclusion of other diseases. Patients were divided into the known clinico-radiological acute encephalopathy syndrome group and unexplained or unclassifiable acute encephalopathy group. Outcomes were assessed by pediatric cerebral performance category (PCPC) score at hospital discharge. Results: Of the 3,802 society members, 217 representing institutions responded, and 39 patients with suspected acute encephalopathy were reported, of which 31 met inclusion criteria. Of these patients, 14 were diagnosed with known clinico-radiological acute encephalopathy syndromes, with acute encephalopathy with biphasic seizures and late reduced diffusion (five patients) being the most common. Five developed acute encephalopathy associated with MIS-C/PIMS. Among 31 patients, 9 (29.0%) had severe sequelae or died (PCPC ≥ 4). Two of three patients with encephalopathy with acute fulminant cerebral edema and two with hemorrhagic shock and encephalopathy syndrome died. The PCPC scores were higher in the known clinico-radiological acute encephalopathy syndrome group than in the unexplained or unclassifiable acute encephalopathy group (P < 0.01). Discussion: Acute encephalopathy related to SARS-CoV-2 infection was demonstrated to be more severe than that caused by other viruses in Japan. Acute encephalopathy syndromes characterized by specific neuroradiological findings was associated with poor clinical outcomes.

Phase Lag Analysis Scalp Electroencephalography May Predict Seizure Frequencies in Patients with Childhood Epilepsy with Centrotemporal Spikes.

Background: Childhood epilepsy with centrotemporal spikes (CECTS) is the most common epilepsy syndrome in school-aged children. However, predictors for seizure frequency are yet to be clarified using the phase lag index (PLI) analyses. We investigated PLI of scalp electroencephalography data at onset to identify potential predictive markers for seizure times. Methods: We compared the PLIs of 13 patients with CECTS and 13 age- and sex-matched healthy controls. For the PLI analysis, we used resting-state electroencephalography data (excluding paroxysmal discharges), and analyzed the mean PLIs among all electrodes and between interest electrodes (C3, C4, P3, P4, T3, and T4) and other electrodes. Furthermore, we compared PLIs between CECTS and control data and analyzed the associations between PLIs and total seizure times in CECTS patients. Results: No differences were detected in clinical profiles or visual electroencephalography examinations between patients with CECTS and control participants. In patients with CECTS, the mean PLIs among all electrodes and toward interest electrodes were higher at the theta and alpha bands and lower at the delta and gamma bands than those in control participants. Additionally, the mean PLIs toward interest electrodes in the beta frequency band were negatively associated with seizure times (P = 0.02). Conclusion: The resting-state delta, theta, alpha, and gamma band PLIs might reflect an aberrant brain network in patients with CECTS. The resting-state PLI among the selected electrodes of interest in the beta frequency band may be a predictive marker of seizure times in patients with CECTS.

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.

Tendency and risk factors of acute pancreatitis in children with severe motor and intellectual disabilities: A single-center study.

OBJECTIVE: Acute pancreatitis (AP) is a life-threatening disease in children with severe motor and intellectual disabilities (SMID). This study aimed to determine the clinical characteristics and causes of AP in children with SMID. METHODS: We enrolled 29 children with AP admitted to our hospital. Patients were divided into children with SMID (AP with SMID group) and the remaining patients (AP without SMID group). All patients in the AP without SMID group had no pre-existing neurological disabilities. We obtained data on the clinical background of patients, severity of AP, treatments, and outcomes. We enrolled 34 children with SMID without a history of AP (SMID control group) to compare their clinical characteristics with the AP with SMID group. We statistically compared the data between the AP with SMID and AP without SMID groups and between the AP with SMID and SMID control groups. RESULT: Compared to the AP without SMID group, the AP with SMID group showed significantly more severe pancreatitis (50% vs 12%) and recurrent pancreatitis (58% vs 18%). Moreover, compared with the SMID control group, the AP with SMID group showed significantly more frequent absence of voluntary movement (83% vs 26%), requirement of respiratory devices (75% vs 35%), panhypopituitarism (33% vs 6%), thermoregulatory dysfunction (58% vs 18%), and low serum albumin levels (3.6 vs 4.1 g/dL). CONCLUSION: AP in children with SMID tended to be associated with severe and recurrent pancreatitis. Children with SMID who had a history of AP had more severe neurological impairment among children with SMID. Hypothalamic-pituitary system dysfunction caused by severe cerebral damage may contribute to the development of AP.

First detailed case report of a pediatric patient with neuronal intranuclear inclusion disease diagnosed by NOTCH2NLC genetic testing.

INTRODUCTION: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease characterized clinically by eosinophilic hyaline intranuclear inclusions in neuronal and other somatic cells. Skin biopsies are reportedly useful in diagnosing NIID, and the genetic cause of NIID was identified as a GGC repeat expansion in NOTCH2NLC in recent years. The number of adult patients diagnosed via genetic testing has increased; however, there have been no detailed reports of pediatric NIID cases with GGC expansions in NOTCH2NLC. This is the first detailed report of a pediatric patient showing various neurological symptoms from the age of 10 and was ultimately diagnosed with NIID via skin biopsy and triplet repeat primed polymerase chain reaction analyses. CASE REPORT: This was an 18-year-old female who developed cyclic vomiting, distal dominant muscle weakness, and sustained miosis at 10 years. Nerve conduction studies revealed axonal degeneration, and her neuropathy had slowly progressed despite several rounds of high-dose methylprednisolone and intravenous immunoglobulin therapy. At 13 years, she had an acute encephalopathy-like episode. At 15 years, brain MRI revealed slightly high-intensity lesions on diffusion-weighted and T2-weighted imaging in the subcortical white matter of her frontal lobes that expanded over time. At 16 years, esophagography, upper gastrointestinal endoscopy, and esophageal manometry revealed esophageal achalasia, and per-oral endoscopic myotomy was performed. At 18 years, we diagnosed her with NIID based on the findings of skin specimen analyses and a GGC repeat expansion in NOTCH2NLC. CONCLUSION: NIID should be considered as a differential diagnosis in pediatric patients with various neurological symptoms.

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.

Quantitative pretreatment EEG predicts efficacy of ACTH therapy in infantile epileptic spasms syndrome.

OBJECTIVE: This study aimed to determine the correlation between outcomes following adrenocorticotrophic hormone (ACTH) therapy and measurements of relative power spectrum (rPS), weighted phase lag index (wPLI), and graph theoretical analysis on pretreatment electroencephalography (EEG) in infants with non-lesional infantile epileptic spasms syndrome (IESS). METHODS: Twenty-eight patients with non-lesional IESS were enrolled. Outcomes were classified based on seizure recurrence following ACTH therapy: seizure-free (F, n = 21) and seizure-recurrence (R, n = 7) groups. The rPS, wPLI, clustering coefficient, and betweenness centrality were calculated on pretreatment EEG and were statistically analyzed to determine the correlation with outcomes following ACTH therapy. RESULTS: The rPS value was significantly higher in the delta frequency band in group R than in group F (p < 0.001). The wPLI values were significantly higher in the delta, theta, and alpha frequency bands in group R than in group F (p = 0.007, <0.001, and <0.001, respectively). The clustering coefficient in the delta frequency band was significantly lower in group R than in group F (p < 0.001). CONCLUSIONS: Our findings demonstrate the significant differences in power and functional connectivity between outcome groups. SIGNIFICANCE: This study may contribute to an early prediction of ACTH therapy outcomes and thus help in the development of appropriate treatment strategies.

Predicting Mathematical Learning Difficulties Using Fundamental Calculative Ability Test (FCAT).

Background: Mathematical learning difficulty (MLD) during school years results from several factors, including dyscalculia. Traditional diagnostic tests for dyscalculia are time intensive and require skilled specialists. This prospective cohort study aimed to reveal that the less time intensive Fundamental Calculative Ability Test (FCAT), administered in first grade, can predict the outcome of mathematical school achievement, which was measured with the curriculum-based mathematical test for second grade (1.2 years after FCAT). Methods: A total of 362 Japanese first- and second-grade children participated. A new quick test measuring fundamental calculative abilities, the FCAT, ordinal, radix, addition, and subtraction, was conducted for the first graders (mean age: 7.1 years). Mathematical school achievement was measured during the tests [mathematics curriculum-based test in Tottori Prefecture (MCBT)] for first (MCBT-1, mean age: 7.3 years) and second graders (MCBT-2, mean age: 8.3 years). We analyzed the associations between FCAT and MCBT-1 and 2 using univariate regression analysis, and cutoff values for mathematical learning difficulty (MLD) at MCBT-2 using the rating operation curve and Youden index. MLD was set as a score of lower than 20% on the MCBT. Results: The FCAT score was significantly associated with the MCBT-1 (regression coefficient: 0.67, P < 0.001) and MCBT-2 scores (regression coefficient: 0.50, P < 0.001). A cutoff value of 47 points (deviation score: 47) at the FCAT score predicted MLD at MCBT-2 (sensitivity: 0.77, specificity: 0.73). For 62 participants with MLD at MCBT-1 score, FCAT scores below the cutoff value of 40 points (deviation score: 35) were at high risk of MLD at MCBT-2 (odds ratio: 6.2). Conclusion: The FCAT is easily conducted in a short time during regular schools and can predict mathematical school achievement. It can be used for the early diagnosis of children with mathematical problems.