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.

Effect of levodopa on pathological gait in Dravet syndrome: A randomized crossover trial using three-dimensional gait analysis.

OBJECTIVE: Individuals with Dravet syndrome (DS) exhibit progressive gait disturbance. No quantitative studies have been conducted to evaluate the effectiveness of medication for gait disturbance. Therefore, the aim of this study was to evaluate the effectiveness of levodopa for pathological gait in people with DS using three-dimensional gait analysis (3DGA). METHODS: Nine individuals with DS, ages 6-20 years, participated in a crossover study of levodopa and were randomly assigned to the levodopa precedence or no levodopa precedence group. Levodopa/carbidopa hydrate was prescribed at a dose of 5 mg/kg/day (body weight <60 kg) or 300 mg/day (body weight ≥60 kg). The medication was taken for 4-6 weeks (4-week washout period). 3DGA was performed three times before the study, with and without levodopa. A mixed-effects model was used to evaluate the effectiveness of levodopa. The primary outcome was the change in the Gait Deviation Index (GDI). In addition, spatiotemporal gait parameters, 6-minute walking distance (6MD), and balance were evaluated. The correlation between the effectiveness of levodopa and age or gait performance before starting levodopa was analyzed. RESULTS: Levodopa improved the GDI by 4.2 points, (p = .029), 6MD by 52 m (p = .002), and balance test result by 4.1 mm (p = .011) in participants with DS. No severe adverse events were observed, with the exception of one participant, who exhibited fever and consequently stopped taking levodopa. Levodopa was more effective in younger participants with a higher baseline gait performance. SIGNIFICANCE: Our randomized crossover trial showed that levodopa has the potential to improve gait disturbance in people with DS.

Endovascular electroencephalography (eEEG) can detect the laterality of epileptogenic foci as accurately as subdural electrodes.

Background: Traditional brain activity monitoring via scalp electroencephalography (EEG) offers limited resolution and is susceptible to artifacts. Endovascular electroencephalography (eEEG) emerged in the 1990s. Despite early successes and potential for detecting epileptiform activity, eEEG has remained clinically unutilized. This study aimed to further test the capabilities of eEEG in detecting lateralized epileptic discharges in animal models. We hypothesized that eEEG would be able to detect lateralization. The purpose of this study was to measure epileptiform discharges with eEEG in animal models with lateralization in epileptogenicity. Materials and methods: We inserted eEEG electrodes into the transverse sinuses of three pigs, and subdural electrodes (SDs) on the surfaces of the left and right hemispheres. We induced epileptogenicity with penicillin in the left brain of pigs F00001 and F00003, and in the right brain of pig F00002. The resulting epileptiform discharges were measured by eEEG electrodes placed in the left and right transverse sinuses, and conducted comparisons with epileptiform discharges from SDs. We also had 12 neurological physicians interpret measurement results from eEEG alone and determine the side (left or right) of epileptogenicity. Results: Three pigs were evaluated for epileptiform discharge detection using eEEG: F00001 (7 months old, 14.0 kg), F00002 (8 months old, 15.6 kg), and F00003 (8 months old, 14.4 kg). The eEEG readings were compared with results from SDs, showing significant alignment across all subjects (p < 0.001). The sensitivity and positive predictive values (PPV) were as follows: F00001 had 0.93 and 0.96, F00002 had 0.99 and 1.00, and F00003 had 0.98 and 0.99. Even though one of the neurological physicians got all sides incorrect, all other assessments were correct. Upon post-experimental dissection, no abnormalities were observed in the brain tissue or in the vascular damage at the site where the eEEG was placed, based on pathological evaluation. Conclusion: With eEEG, lateralization can be determined with high sensitivity (>0.93) and PPV (>0.95) that appear equivalent to those of subdural EEG in the three pigs. This lateralization was also discernible by neurological physicians on visual inspection.

A child with TSC2/PKD1 contiguous gene deletion syndrome successfully treated with tolvaptan for rapidly enlarging renal cysts.

Tolvaptan, a vasopressin receptor antagonist, has been shown to be effective in the treatment of renal cysts in ADPKD. However, tolvaptan is not indicated for pediatric patients, and reports of its use are rare, making its efficacy and adverse reactions unclear. Herein, we present the case of an 11-year-old girl who had vitiligo from birth. She was diagnosed with West syndrome at 6 months of age and tuberous sclerosis at 2 years of age. At the age of 6 years, an abdominal magnetic resonance imaging (MRI) revealed multiple bilateral renal cysts, and she was diagnosed with ADPKD. Abdominal MRI scans performed at 10 years and 11 years showed rapid renal cyst enlargement, and the renal prognosis was judged to be poor. The patient was treated with tolvaptan to delay cyst exacerbation. There were no apparent adverse events after the initiation of treatment, and the MRI performed 12 months after treatment initiation showed that renal cyst enlargement was suppressed. The results suggest that tolvaptan may be effective in pediatric patients with severe ADPKD who have rapidly enlarging renal cysts, although evaluation of renal cyst enlargement and side effects should be continued.

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.

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.

Non-1st seizure was less severe than 1st seizure with non-urgent level among suspected seizures transferred by ambulance.

BACKGROUND: To prioritize emergency medical calls for ambulance transport for patients with suspected seizures, information about whether the event is their 1st or non-1st seizure is important. However, little is known about the difference between 1st and non-1st seizures in terms of severity. We hypothesized that patients transferred multiple times (≥2 times) would represent a milder scenario than patients on their first transfer. The purpose of this study was to compare patients with suspected seizures on 1st transfer by ambulance and patients who had been transferred ≥2 times. METHODS: We statistically compared severity of suspected seizures between two groups of patients with suspected seizures transferred between December 2014 and November 2019 (before the coronavirus disease 2019 pandemic) to our facility by ambulance for either the first time (1st Group) or at least the second time (Non-1st Group). Severity categories were defined as: Level 1 = life-threatening; Level 2 = emergent, needing admission to the intensive care unit; Level 3 = urgent, needing admission to a hospital general ward; Level 4 = less urgent, needing intervention but not hospitalization; and Level 5 = non-urgent, not needing intervention. RESULTS: Among 5996 patients with suspected seizures conveyed to the emergency department by ambulance a total of 14,263 times during the study period, 1222 times (8.6%) and 636 patients (11%) met the criteria. Severity grade of suspected seizures ranged from 1 to 5 (median, 4; interquartile range, 3-4) for the 1st Group and from 1 to 5 (median, 5; interquartile range, 4-5) for the Non-1st Group. Most severe grade ranged from 1 to 5 (median, 4; interquartile range, 4-5) for the Non-1st Group. Severity grade differed significantly between groups (p < 0.001, Mann-Whitney U-test). Uni- and multivariate logistic regression tests also suggested a significant difference (p < 0.001) in severity grades. CONCLUSION: In direct comparisons, grade of suspected seizure severity was lower in the Non-1st Group than in the 1st Group.

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.

Clinical Practice Guidelines for tuberous sclerosis complex-associated renal angiomyolipoma by the Japanese Urological Association: Summary of the update.

New clinical issues have been raised through an interval of 7 years from the previous version (2016). In this study, we update the "Clinical Practice Guidelines for tuberous sclerosis complex-associated renal angiomyolipoma" as a 2023 version under guidance by the Japanese Urological Association. The present guidelines were cooperatively prepared by the Japanese Urological Association and Japanese Society of Tuberous Sclerosis Complex; committee members belonging to one of the two societies or specializing in the treatment of this disease were selected to prepare the guidelines in accordance with the "Guidance for preparing treatment guidelines" published by Minds (2020 version). The "Introduction" consisted of four sections, "Background Questions (BQ)" consisted of four sections, "Clinical Questions (CQ)" consisted of three sections, and "Future Questions (FQ)" consisted of three sections (total: 14 sections). Concerning CQ, an agreement was confirmed through voting by the committee members based on the direction and strength of recommendation, accuracy of evidence, and recommendation comments. The present guidelines were updated based on the current evidence. We hope that the guidelines will provide guiding principles for the treatment of tuberous sclerosis complex-associated renal angiomyolipoma to many urologists, becoming a foundation for subsequent updating.

Finger movement functions remain in the ipsilesional hemisphere and compensation by the contralesional hemisphere might not be expected after hemispherotomy -pre- and post-hemispherotomy evaluations in 8 cases.

BACKGROUND: We hypothesized that fine finger motor functions are controlled by the ipsilesional hemisphere, and that gross motor functions are compensated for by the contralesional hemisphere after brain injury in humans. The purpose of this study was to compare finger movements before and after hemispherotomy that defunctionated the ipsilesional hemisphere for patients with hemispherical lesions. METHODS: We statistically compared Brunnstrom stage of the fingers, arm (upper extremity), and leg (lower extremity) before and after hemispherotomy. Inclusion criteria for this study were: 1) hemispherotomy for hemispherical epilepsy; 2) a ≥ 6-month history of hemiparesis; 3) post-operative follow-up ≥ 6 months; 4) complete freedom from seizures without aura; and 5) application of our protocol for hemispherotomy. RESULTS: Among 36 patients who underwent multi-lobe disconnection surgeries, 8 patients (2 girls, 6 boys) met the study criteria. Mean age at surgery was 6.38 years (range, 2-12 years; median, 6 years; standard deviation, 3.5 years). Paresis of the fingers was significantly exacerbated (p = 0.011) compared to pre-operatively, whereas that of the upper limbs (p = 0.07) and lower limbs (p = 0.103) was not. CONCLUSION: Finger movement functions tend to remain in the ipsilesional hemisphere after brain injury, whereas gross motor movement functions such as those of the arms and legs are compensated for by the contralesional hemisphere in humans.

An integrated genetic analysis of epileptogenic brain malformed lesions.

Focal cortical dysplasia is the most common malformation during cortical development, sometimes excised by epilepsy surgery and often caused by somatic variants of the mTOR pathway genes. In this study, we performed a genetic analysis of epileptogenic brain malformed lesions from 64 patients with focal cortical dysplasia, hemimegalencephy, brain tumors, or hippocampal sclerosis. Targeted sequencing, whole-exome sequencing, and single nucleotide polymorphism microarray detected four germline and 35 somatic variants, comprising three copy number variants and 36 single nucleotide variants and indels in 37 patients. One of the somatic variants in focal cortical dysplasia type IIB was an in-frame deletion in MTOR, in which only gain-of-function missense variants have been reported. In focal cortical dysplasia type I, somatic variants of MAP2K1 and PTPN11 involved in the RAS/MAPK pathway were detected. The in-frame deletions of MTOR and MAP2K1 in this study resulted in the activation of the mTOR pathway in transiently transfected cells. In addition, the PTPN11 missense variant tended to elongate activation of the mTOR or RAS/MAPK pathway, depending on culture conditions. We demonstrate that epileptogenic brain malformed lesions except for focal cortical dysplasia type II arose from somatic variants of diverse genes but were eventually linked to the mTOR pathway.

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.