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OBJECTIVE To investigate the usefulness of procalcitonin (PCT) as predictive factors of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease patients. METHODS We retrospectively analyzed the laboratory data from 215 children with Kawasaki disease treated with IVIG from 2014 to 2019. We analyzed the clinical and laboratory parameters just before the IVIG including serum levels of PCT with respect to the IVIG response. RESULTS Eventually, 127 patients were analyzed. The median age was 2.4 years. IVIG was effective in 108 children (responders) and was ineffective in 19 (non-responders). Serum PCT concentration was higher in non-responders than those of responders (P < 0.001). Multivariate logistic regression analyses indicated that higher PCT concentration (odds ratio 1.34, 95% confidence interval 1.10-1.64) were associated with IVIG resistance. Analyses of the receiver operating characteristic curve showed that the cutoff value of PCT 2.18 ng/mL had 46.4% of sensitivity and 93.9% of specificity. Receiver operating characteristic analysis yielded an area under the curve of 0.82 (0.72-0.92) to predict IVIG resistance. CONCLUSIONS Serum PCT value can be an excellent biomarker for predicting unresponsiveness to IVIG with a good discriminatory ability as well as the existing prediction scores.

Objectives Preterm children with severe dyskinetic cerebral palsy due to bilirubin encephalopathy often suffer from marked generalised hypertonus as they age. We performed a questionnaire survey to investigate patient-reported outcomes of treatments for improving their activities of daily life. Methods A mail questionnaire was administered to the caregivers of 67 children with preterm bilirubin encephalopathy aged >4 years. We asked about the type of treatments they received and their efficacy using a five-point subjective scale for the following five domains: motor function, postural stability, sleep, pain, and care burden. The names of oral drugs and their efficacies were also explored. Results The response rate of the questionnaires was 62.7% (42/67), and we analysed the results from 41 validated cases. All children underwent rehabilitation. A total of 30 children received oral drugs, 22 botulinum toxin, 12 orthopaedic surgery, and 3 intrathecal baclofen. Each of these treatments was subjectively reported to be effective in more than half of the recipients for each of the five domains, whereas 23 (56%) required more than two types of treatments other than rehabilitation. Chlordiazepoxide was the most commonly used oral drug, by 28 children (68%), and was discontinued in 7 patients (25%) only. In the sleep domain, the rate of a positive effect was significantly higher for oral drugs (92.7%) than the other treatments (p Conclusion All treatments were partially effective, but their appropriate combination based on a multidisciplinary approach is essential for muscle tone management in children with preterm bilirubin encephalopathy.

Background An outbreak of acute flaccid myelitis was chronologically correlated with an outbreak of severe respiratory illness in Japan in 2015. We hypothesized that increases in children hospitalized with severe respiratory illnesses might also be associated with increase in acute flaccid myelitis in autumn 2018. Methods We explored the temporal correlations between respiratory illness outbreaks and acute flaccid myelitis during autumn season between 2016 and 2018 using questionnaire surveys. One questionnaire explored the monthly numbers of children with acute flaccid myelitis, Guillain-Barre syndrome, and other acute flaccid paralyses. The other questionnaire explored the monthly numbers of children hospitalized with respiratory illnesses associated with wheezing. A correlation between the monthly numbers of children with acute flaccid myelitis and those with respiratory illness was analyzed using the Pearson correlation test. Results Although the number of patients hospitalized with respiratory illness did not correlate with the number of those admitted with myelitis, increases in children aged 7-12 and 13-19 years requiring intensive care unit admission correlated temporally with an outbreak of acute flaccid myelitis. Conclusions An increase in intensive care unit admissions to treat respiratory disease occurred in association with a cluster of acute flaccid myelitis. An increase in the number of intensive care unit admissions due to respiratory illness may be a clue to expect the occurrence of acute flaccid myelitis.

For preterm and very low birthweight infants, the mother’s own milk is the best nutrition. Based on the latest information for mothers who give birth to preterm and very low birthweight infants, medical staff should encourage and assist mothers to pump or express and provide their own milk whenever possible.If the supply of maternal milk is insufficient even though they receive adequate support, or the mother’s own milk cannot be given to her infant for any reason, donor human milk should be used.Donors who donate their breast milk need to meet the Guideline of the Japan Human Milk Bank Association.Donor human milk should be provided according to the medical needs of preterm and very low birthweight infants, regardless of their family’s financial status.In the future, it will be necessary to create a system to supply an exclusive human milk‐based diet (EHMD), consisting of human milk with the addition of a human milk‐derived human milk fortifier, to preterm and very low birthweight infants.

BACKGROUND Distributions of serum pepsinogen (PG) values were assessed in Helicobacter pylori-infected and non-infected junior high school students (aged 12-15 years) in Japan. METHODS All junior high school students (1,225 in total) in Sasayama city, who were basically healthy, were asked to provide urine and serum samples, which were used to measure urine and serum H. pylori antibodies using ELISA kits and PG values. The subjects, whose urine and serum antibodies were both positive, were considered H. pylori infected. RESULTS Of the 187 subjects who provided urine and blood samples, 8 were infected, 4 had discrepant results, 4 had negative serum antibody titers no less than 3.0 U/ml, and 171 were non-infected. In the H. pylori non-infected subjects, the median PG I and PG II values and PG I to PG II ratio (PG I/II) were 40.8 ng/mL, 9.5 ng/mL, and 4.4, respectively, whereas in the infected subjects, these values were 55.4 ng/mL, 17.0 ng/mL, and 3.3, respectively (each P < 0.01). In the non-infected subjects, PG I and PG II were significantly higher in males than in females (P < 0.01). CONCLUSIONS The PG I and PG II values were higher, and the PG I/II was lower in H. pylori infected students than in non-infected students. In H. pylori non-infected students, males showed higher PG I and PG II values than females. The distributions of PG values in junior high school students differed from those in adults.

BACKGROUND Carnitine plays an essential role in transfer of long-chain fatty acids to mitochondria for β-oxidation. No studies have characterized carnitine in children with Kawasaki disease (KD). The objective of this study is to clarify the characteristics of serum free carnitine (FC) in hospitalized pediatric patients with KD. METHODS We retrospectively analyzed 45 patients with KD in whom serum FC levels were measured. We investigated the clinical and laboratory parameters before the intravenous immunoglobulin including serum FC levels according to the response to intravenous immunoglobulin. We also analyzed the relation between serum FC, and laboratory data and clinical variables. RESULTS Intravenous immunoglobulin was effective in 33 children (responders) and was ineffective in 12 (non-responders). The serum FC levels were higher in non-responders than in responders: 35.3 μmol/L (range, 26.8-118.4 μmol/L) vs 31.4 μmol/L (range, 20.9-81.2 μmol/L), p

Recently, whole-exome sequencing (WES) has been used for genetic diagnoses of patients who remain otherwise undiagnosed. WES was performed in 177 Japanese patients with undiagnosed conditions who were referred to the Tokai regional branch of the Initiative on Rare and Undiagnosed Diseases (IRUD) (TOKAI-IRUD). This study included only patients who had not previously received genome-wide testing. Review meetings with specialists in various medical fields were held to evaluate the genetic diagnosis in each case, which was based on the guidelines of the American College of Medical Genetics and Genomics. WES identified diagnostic single-nucleotide variants in 66 patients and copy number variants (CNVs) in 11 patients. Additionally, a patient was diagnosed with Angelman syndrome with a complex clinical phenotype upon detection of a paternally derived uniparental disomy (UPD) [upd(15)pat] wherein the patient carried a homozygous DUOX2 p.E520D variant in the UPD region. Functional analysis confirmed that this DUOX2 variant was a loss-of-function missense substitution and the primary cause of congenital hypothyroidism. A significantly higher proportion of genetic diagnoses was achieved compared to previous reports (44%, 78/177 vs. 24–35%, respectively), probably due to detailed discussions and the higher rate of CNV detection.

We performed a retrospective survey and verification of the medical records of death cases of children (and adolescents; aged18 years) between 2014 and 2016 in pediatric specialty training facilities in Japan. Of the 2,827 registered cases at 163 facilities, 2,348 cases were included. The rate of identified deaths compared with the demographic survey, was 18.2%-21.0% by age group. The breakdown of deaths was determined as follows: 638 cases (27.2%) were due to external factors or unknown causes, 118 (5.0%) were suspected to involve child maltreatment, 932 (39.7%) were of moderate or high preventability or were indeterminable. Further detailed verification was required for 1,333 cases (56.8%). Comparison of the three prefectures with high rates of identified deaths in Japan revealed no significant differences, such as in the distribution of diseases, suggesting that there was little selection bias. The autopsy rate of deaths of unknown cause was 43.4%, indicating a high ratio of forensic autopsies. However, sufficient clinical information was not collected; therefore, thorough evaluations were difficult to perform. Cases with a moderate or high possibility of involvement of child maltreatment accounted for 5%, similar to previous studies. However, more objective evaluation is necessary. Preventable death cases including potentially preventable deaths accounted for 25%, indicating that proposals need to be made for specific preventive measures. Individual primary verification followed by secondary verification by multiple organizations is effective. It is anticipated that a child death review (CDR) system with such a multi-layered structure will be established; however, the following challenges were revealed: The subjects of CDR are all child deaths. Even if natural death cases are entrusted to medical organizations, and complicated cases to other special panels, the numbers are very high. Procedures need to be established to sufficiently verify these cases. Although demographic statistics are useful for identifying all deaths, care must be taken when interpreting such data. Detailed verification of the cause of death will affect the determination of subsequent preventability. Verification based only on clinical information is difficult, so a procedure that collates non-medical information sources should be established. It is necessary to organize the procedures to evaluate the involvement of child maltreatment objectively and raise awareness among practitioners. To propose specific preventive measures, a mechanism to ensure multiprofessional diverse perspectives is crucial, in addition to fostering the foundation of individual practitioners. To implement the proposed measures, it is also necessary to discuss the responsibilities and authority of each organization. Once the CDR system is implemented, verification of the system should be repeated. Efforts to learn from child deaths and prevent deaths that are preventable as much as possible are essential duties of pediatricians. Pediatricians are expected to undertake the identified challenges and promote and lead the implementation of the CDR system. This is a word-for-word translation of the report in J. Jpn. Pediatr. Soc. 2019; 123 (11): 1736-1750, which is available only in the Japanese language.

To investigate the usefulness of quenching probe polymerase chain reaction (Q-probe PCR) for detection of macrolides-resistant Mycoplasma pneumoniae (MP), we retrospectively analyzed the clinical course of 21 children with MP infection. The rate of macrolides resistant MP was 66.7%. The duration of pyrexia after the initial antibiotics treatment was longer in patients with macrolides-resistant MP infection than in those with macrolides-sensitive MP infection. The duration of pyrexia after Q-probe PCR was not significantly different between patients with macrolides-resistant MP infection and those with macrolides-sensitive MP infection. These results suggest that antibiotic use based on Q-probe PCR will reduce duration of pyrexia. Q-probe PCR contributes to determine appropriate antibiotics and to improve the clinical course of MP infections.

Background We aimed to investigate electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) findings to elucidate the interictal epileptiform discharge (IED)-related functional alterations in deep brain structures as well as the neocortex in childhood epilepsy with centrotemporal spikes (CECTS). Methods Ten children with CECTS (median age; 8.2 years) referred to our hospital within a year of onset were eligible for inclusion. They underwent EEG-fMRI recording during sleep. In addition, longitudinal evaluations, including medical examinations, intelligence tests, and questionnaires about developmental disabilities, were performed. The initial evaluation was performed at the same time as the EEG-fMRI, and the second evaluation was performed over 2 years after the initial evaluation. Results Three children were unable to maintain sleep during the EEG-fMRI recording, and the remaining seven children were eligible for further assessment. All patients showed unilateral-dominant centrotemporal spikes during scans. One patient had only positive hemodynamic responses, while the others had both positive and negative hemodynamic responses. All patients showed IED-related hemodynamic responses in the bilateral neocortex. For deep brain structures, IED-related hemodynamic responses were observed in the cingulate gyrus (n=4), basal ganglia (n=3), thalamus (n=2), and default mode network (n=1). Seizure frequencies at the second evaluation were infrequent or absent, and the longitudinal results of intelligence tests and questionnaires were within normal ranges. Conclusions We demonstrated that IEDs affect broad brain areas, including deep brain structures such as cingulate gyrus, basal ganglia, and thalamus. Deep brain structures may play an important role in the pathophysiology of CECTS.

This multicenter study examined the effectiveness and tolerability of lacosamide (LCM) for children and young adults with epilepsy, particularly in patients who had previously been treated with other sodium channel blockers (SCBs) and the difference in effectiveness and tolerability when using other concomitant SCBs.We retrospectively studied the clinical information of patients aged30 years given LCM to treat epilepsy. The effectiveness and adverse events (AEs) of LCM and the other SCBs were investigated. Factors related to the effectiveness and AEs of LCM, such as the number of antiepileptic drugs (AEDs) tried before LCM and concomitantly used SCBs, were also studied.We enrolled 112 patients (median age = 11 years). One year after starting LCM, 29% of the patients were seizure free, and 50% had a ≥50% seizure reduction. Of the patients, 17% experienced AEs, the most common being somnolence. A ≥50% seizure reduction was observed for LCM in 30% of patients in whom other SCBs had not been effective. Lacosamide produced a ≥50% seizure reduction in 35% of the patients taking one concomitant SCB. By contrast, no patients had ≥50% seizure reduction, and 33% developed AEs, when LCM was administered concomitantly with two SCBs.Lacosamide was effective in 30% of children and young adults in whom other SCBs had not been effective. The effectiveness of LCM may differ from that of other SCBs, and it is worth trying in patients with epilepsy resistant to other AEDs.

Objective To unveil current medical and psychosocial conditions of patients with West syndrome in Japan. Methods A cross-sectional analysis was performed in patients with West syndrome registered in the Rare Epilepsy Syndrome Registry (RES-R) of Japan. Furthermore, new-onset patients registered in the RES-R were observed prospectively and their outcomes after one and two years of follow-up were compared with data at onset. Results For the cross-sectional study, 303 patients with West syndrome were included. Seizures (such as spasms, tonic seizures and focal seizures) occurred daily in 69.3% of the patients at registration. Seizure frequency of less than one per year was observed in cases of unknown etiology (22.6%), genetic etiology (23.8%) and malformation of cortical development (MCD; 19.1%). Neurological findings were absent in 37.0%, but a high rate of abnormality was seen in patients with Aicardi syndrome, hypoxic-ischemic encephalopathy (HIE), genetic etiology and MCD other than focal cortical dysplasia, accompanied by a >50% rate of bedridden patients. Abnormal EEG was found in 96.7%, and CT/MRI was abnormal in 62.7%. Treatments included antiepileptic drug therapy (94.3%), hormonal therapy (72.6%), diet therapy (8.3%) and surgery (15.8%). Intellectual/developmental delay was present in 88.4%, and was more severe in patients with Aicardi syndrome, genetic etiology and HIE. Autism spectrum disorder was found in 13.5%. For the longitudinal study, 27 new-onset West syndrome patients were included. The follow-up study revealed improved seizure status after two years in 66.7%, but worsened developmental status in 55.6%, with overall improvement in 51.9%. Significance The study reveals the challenging neurological, physical and developmental aspects, as well as intractable seizures, in patients with West syndrome. More than a half of the children showed developmental delay after onset, even though seizures were reduced during the course of the disease.

To investigate the usefulness of quenching probe polymerase chain reaction (Q-probe PCR) for the detection of macrolide-resistant Mycoplasma pneumoniae (MP), we retrospectively analyzed the clinical course of 21 children with MP infection. The rate of macrolide-resistant MP was 66.7%. The duration of pyrexia after the initial antibiotic treatment was longer in patients with macrolide-resistant MP infection than in those with macrolide-sensitive MP infection. The duration of pyrexia after Q-probe PCR was not significantly different between patients with macrolide-resistant and -sensitive MP infection. Antibiotic use based on qPCR may reduce the duration of pyrexia. Q-probe PCR is useful in determining the appropriate antibiotics and improves the clinical course of MP infections.

Background Glucocorticoids rarely cause anaphylaxis. Common methods for the determination of allergens include in vivo skin prick test (SPT) and intradermal skin test (IDST) and the in vitro basophil activation test (BAT). However, to our knowledge, the best strategy for diagnosing glucocorticoid-induced anaphylaxis has not been elucidated. Case presentation A 10-year-old boy was admitted to our hospital because of 2 weeks of fever and arthralgia. He had not been treated with glucocorticoids before, including methylprednisolone (mPSL). He was suspected to have bacterial myositis and was treated with ceftriaxone. However, his symptoms persisted for > 2 weeks. Autoinflammatory arthritis was suspected, and he was treated with mPSL sodium succinate (MPS) pulse therapy (30 mg/kg). After 15 min of mPSL injection, he had wheezing and generalized wheal formation with decreased oxygen saturation. As anaphylaxis was suspected, mPSL was discontinued, and olopatadine and oxygen were administered. The symptoms improved considerably without the use of epinephrine and disappeared in 30 min. One month after discharge, SPT, IDST, and BAT were performed without discontinuing his prescribed oral prednisolone. SPTs for MPS, hydrocortisone sodium succinate (HCS), prednisolone sodium succinate (PSS), dexamethasone sodium phosphate (DSP), and betamethasone sodium phosphate (BSP) were negative. IDSTs for MPS, HCS, and PSS were positive, whereas those for DSP and BSP were negative. By contrast, BATs for MPS, HCS, and PSS were negative. Although glucocorticoid-induced hypersensitivity caused by nonmedicinal ingredients such as lactose, carboxymethylcellulose, polyethylene glycol, and hexylene glycol has been reported; the glucocorticoids tested in this patient did not contain any of these nonmedicinal ingredients. As the glucocorticoids that were positive on IDST share a succinate ester, this might have caused MPS-induced anaphylaxis. Conclusions We report the case of MPS-induced anaphylaxis diagnosed by IDST but not BAT. In case reports of glucocorticoid-induced anaphylaxis in the literature, most patients were diagnosed with SPT or IDST. These results suggest that BAT should be considered when IDST and SPT are negative. Further studies are necessary to clarify the best strategy for diagnosing glucocorticoid-induced anaphylaxis.

Purpose This study was performed to clarify the clinical features of Japanese patients with PRRT2 mutations. Methods The PRRT2 gene was analyzed in 135 patients with benign infantile epilepsy (BIE) or paroxysmal kinesigenic dyskinesia (PKD) using a direct sequencing method: 92 patients had BIE alone, 25 had both BIE and PKD, and 18 had PKD alone. Of the cases, 105 were familial, and 30 were sporadic. Clinical information was collected using a structured questionnaire. Results PRRT2 mutations were identified in 104 patients. Among the familial cases, PRRT2 mutations were found in at least one individual in 21 of 28 families with BIE alone, in 26 of 27 families with infantile convulsions and choreoathetosis, and in 2 of 3 families with PKD alone. Among the sporadic cases, PRRT2 mutations were observed in 7 of 25 patients with BIE alone, in 1 of 1 patient with BIE and PKD, and in 3 of 4 patients with PKD alone. The c.649dupC mutation was the most frequent, followed by the c.981C > G mutation. Among the patients with epilepsy, the median age at BIE onset was 5 months, the median age at the last seizure was 6 months, and the median number of seizures was 5. Conclusion PRRT2 mutations were found in 68% of Japanese probands with BIE or PKD. The phenotypes of BIE associated with PRRT2 mutations were consistent with those of BIE diagnosed clinically.

Background Recently, many genes related to neurodevelopmental disorders have been identified by high-throughput genomic analysis; however, a comprehensive understanding of the mechanism underlying neurodevelopmental disorders remains to be established. To further understand these underlying mechanisms, we performed a comprehensive genomic analysis of patients with undiagnosed neurodevelopmental disorders. Methods Genomic analysis using next-generation sequencing with a targeted panel was performed for a total of 133 Japanese patients (male/female, 81/52) with previously undiagnosed neurodevelopmental disorders, including developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), and epilepsy. Genomic copy numbers were also analyzed using the eXome Hidden Markov Model (XHMM). Results Thirty-nine patients (29.3%) exhibited pathogenic or likely pathogenic findings with single-gene variants or chromosomal aberrations. Among them, 20 patients were presented here. Pathogenic or likely pathogenic variants were identified in 18 genes, including ACTG1, CACNA1A, CHD2, CDKL5, DNMT3A, EHMT1, GABRB3, GABRG2, GRIN2B, KCNQ3, KDM5C, MED13L, SCN2A, SHANK3, SMARCA2, STXBP1, SYNGAP1, and TBL1XR1. Conclusion A diagnostic yield of 29.3% in this study was nearly the same as that previously reported from other countries. Thus, we suggest that there is no difference in genomic backgrounds in Japanese patients with undiagnosed neurodevelopmental disabilities. Although most of the patients possessed de novo variants, one of the patients showed an X-linked inheritance pattern. As X-linked recessive disorders exhibit the possibility of recurrent occurrence in the family, comprehensive molecular diagnosis is important for genetic counseling.

The objective of this study was to describe a novel amplitude-integrated electroencephalography (aEEG) pattern in infants with hypoxic–ischemic encephalopathy (HIE) and to assess the clinical significance. The aEEG traces of infants with HIE who were treated with therapeutic hypothermia (TH) from 2012 to 2017 were analyzed. A pseudo-sawtooth (PST) pattern was defined as a periodic increase of the upper and/or lower margin of the trace on aEEG without showing seizure activities on conventional EEG (CEEG). Of the 46 infants, 6 (13%) had the PST pattern. The PST pattern appeared following a flat trace or a continuous low-voltage pattern and was followed by a burst-suppression pattern. On CEEG, the PST pattern consists of alternating cycles of low-voltage irregular activities and almost flat tracing. The PST pattern was associated with neuroimaging abnormalities and with various degrees of neurodevelopmental outcomes. Positive predictive values of the PST or worse pattern for adverse outcomes were high at 12 h after birth. A novel aEEG background pattern in infants with HIE was reported. The PST pattern likely indicates a suppressed background pattern and may be linked to unfavorable outcomes. Further multicenter validation study is needed to clarify its clinical significance.

Background The secular trend in the prevalence of Helicobacter pylori (H. pylori) infection among children and adolescents in Japan has not been well documented. Materials and Methods We reviewed all relevant literature published between 1991 and 2017, focusing on the relationship between the prevalence of H. pylori infection and birth year. Our literature search covered all journal articles, conference proceedings and meeting abstracts that reported the prevalence of H. pylori infection in Japanese subjects under 20 years of age. Results We examined the prevalence of H. pylori infection according to birth year on the basis of data points, which comprised 20,269 subjects of 81 groups. Three-coefficient logistic regression analysis was performed to examine the trend in H. pylori prevalence. The prevalence was approximately 10% in the individuals born in 1985, but it decreased to 3% in the individuals born in 2011. The plot of H. pylori prevalence against birth year clearly indicated a birth-cohort effect: the earlier the birth year, the higher the prevalence. Conclusions Our analysis revealed a rapidly decreasing prevalence of H. pylori infection among Japanese children and adolescents over the past three decades.

Objective The aim of this study was to clarify the effects of antihistamines on the semiology of febrile seizures. Methods The manifestations of febrile seizures were recorded using a structured questionnaire immediately after patients arrived at the hospital. We focused on events at seizure commencement, including changes in behavior and facial expression, and ocular and oral symptoms. The presence or absence of focal and limbic features was determined for each patient. Drugs taken within 6 h prior to seizure were noted. Seizure manifestations were compared between children who did not take antihistamines and those who took antihistamines. Results Seizures lasting ≥5 min were relatively more frequent in children who did not take antihistamines, although the difference was not statistically significant. One or more focal features were present in 60 of 78 children with no antihistamines and 17 of 23 children with antihistamines. One or more limbic features were present in 32 of 78 children with no antihistamines and 9 of 23 children with antihistamines. No significant difference in the numbers of focal or limbic features was apparent between children who did not take antihistamines and those who took antihistamines. Conclusion Antihistamines did not significantly affect the semiology of febrile seizures.

BACKGROUND Very limited data are available on childhood gastric cancer. Using a retrospective survey and literature review, we assessed the clinical features of gastric cancer in children and adolescents. METHODS We collected information on childhood gastric cancer from pediatricians of 518 hospitals that issue the title of "certified board pediatrician" approved by Japan Pediatric Society, using a questionnaire on background, diagnosis year, onset symptoms, tumor location, histology, nodular gastritis, Helicobacter pylori testing, treatment, and prognosis. Studies were collected using PubMed and the NPO Japan Medical Abstracts Society database. Data for childhood gastric cancer were abstracted from the Japanese Vital Statistics database. RESULTS Of the 518 hospitals, 349 returned the questionnaire, which identified four patients. Literature review identified 77 cases of gastric cancer, and we analyzed data for 80 children 10 years old, and there were no sex differences. Onset symptoms ranged from abdominal pain to non-localized. Sixteen of 44 children had a family history of cancer; 10 had a family history of gastric cancer. Histologically, approximately 80% had undifferentiated-type carcinoma. Prognosis was extremely poor, and two of three tested children were positive for H. pylori infection. Childhood gastric cancer death has been declining. CONCLUSIONS Childhood gastric cancer is rare in Japan, and information on H. pylori in childhood gastric cancer patients is limited. Declining childhood gastric cancer rates may reflect the decreasing prevalence of infection but further study is necessary to clarify the relationship between H. pylori and gastric cancer.

Purpose We evaluated the diagnostic accuracy of insulin-like growth factor-1 (IGF-1) for screening growth hormone deficiency (GHD) to determine the usefulness of IGF-1 as a screening test. Methods Among 298 consecutive children who had short stature or decreased height velocity, we measured IGF-1 levels and performed growth hormone (GH) secretion test using clonidine, arginine, and, in cases with different results of the two tests, L-dopa. Patients with congenital abnormalities were excluded. GHD was defined as peak GH ≤ 6.0 ng/mL in the two tests. Results We identified 60 and 238 patients with and without GHD, respectively. The mean IGF-1 (SD) was not significantly different between the GHD and non-GHD groups (p = 0.23). Receiver operating characteristic curve analysis demonstrated the best diagnostic accuracy at an IGF-1 cutoff of −1.493 SD, with 0.685 sensitivity, 0.417 specificity, 0.25 positive and 0.823 negative predictive values, and 0.517 area under the curve. Correlation analysis revealed that none of the items of patients’ characteristics increased the diagnostic power of IGF-1. Conclusion IGF-1 level had poor diagnostic accuracy as a screening test for GHD. Therefore, IGF-1 should not be used alone in the screening of GHD. A predictive biomarker for GHD should be developed in the future.

We evaluated the diagnostic accuracy of insulin-like growth factor-1 (IGF-1) for screening growth hormone deficiency (GHD) to determine the usefulness of IGF-1 as a screening test. Among 298 consecutive children who had short stature or decreased height velocity, we measured IGF-1 levels and performed growth hormone (GH) secretion test using clonidine, arginine, and, in cases with different results of the two tests, L-dopa. Patients with congenital abnormalities were excluded. GHD was defined as peak GH ≤ 6.0 ng/mL in the two tests. We identified 60 and 238 patients with and without GHD, respectively. The mean IGF-1 standard deviation (SD) was not significantly different between the GHD and non-GHD groups (p = 0.23). Receiver operating characteristic curve analysis demonstrated the best diagnostic accuracy at an IGF-1 cutoff of − 1.493 SD, with 0.685 sensitivity, 0.417 specificity, 0.25 positive and 0.823 negative predictive values, and 0.517 area under the curve. Correlation analysis revealed that none of the items of patients’ characteristics increased the diagnostic power of IGF-1. IGF-1 level had poor diagnostic accuracy as a screening test for GHD. Therefore, IGF-1 should not be used alone for GHD screening. A predictive biomarker for GHD should be developed in the future.

Purpose We evaluated the diagnostic accuracy of insulin-like growth factor-1 (IGF-1) for screening growth hormone deficiency (GHD) to determine the usefulness of IGF-1 as a screening test. Methods On 298 consecutive children who had short stature or decreased height velocity, we measured IGF-1 levels and performed growth hormone (GH) secretion test using clonidine, arginine, and, in cases with different results of the two tests, L-dopa. Patients with congenital abnormalities were excluded. GHD was defined as peak GH ≤ 6.0 ng/mL in the two tests. Results We identified 60 and 238 patients with and without GHD, respectively. The mean IGF-1 (SD) was not significantly different between the GHD and non-GHD groups (p = 0.23). Receiver operating characteristic curve analysis demonstrated the best diagnostic accuracy at an IGF-1 cutoff of −1.493 SD, with sensitivity of 0.685, specificity of 0.417, positive predictive value of 0.25, negative predictive value of 0.823, and area under the curve of 0.517. Spearman’s rank correlation coefficient showed that IGF-1 (SD) was weakly correlated with age, bone age, height velocity before examination, weight (SD), and BMI (SD) and very weakly correlated with height (SD), target height (SD), and maximum GH peak. Conclusion IGF-1 level had poor diagnostic accuracy as a screening test for GHD. Correlation analysis revealed that none of the items increased the diagnostic power of IGF-1. Therefore, IGF-1 should not be used alone in the screening of GHD. A predictive biomarker for GHD should be developed in the future.

BACKGROUND Antenatal magnesium sulfate (MgSO4 ) has been used in mother, but the influence of MgSO4 on the fetus is unclear. The purpose of this study is to determine whether longer antenatal MgSO4 exposure correlates with adverse effects in newborns. METHODS The clinical data of 77 infants born to mothers treated with MgSO4 were collected. The infants were divided into two groups according to the serum Mg concentration, cumulative Mg dose, and duration of maternal antenatal Mg treatment. RESULTS The serum Mg level of the infants correlated with that of the mothers but not with the duration of Mg treatment or the cumulative dose of Mg. There were no significant differences in the infants' clinical variables according to either the duration of Mg treatment or the cumulative dose of Mg. By contrast, enteral feeding tolerance began at a significantly later age and the heart rate on admission was significantly lower in infants with a serum Mg level ≥ 4.0 mmol/l than in those with a serum Mg level < 4.0 mmol/l. CONCLUSIONS Modest effects on the clinical variables of infants with higher serum Mg levels were determined, whereas neither the duration of Mg treatment nor the cumulative Mg dose correlated with the clinical variables of the infants. Thus, in newborns with only moderately elevated serum Mg levels serious adverse effects are unlikely.

Repetitive sleep starts (RSS) are clusters of nonepileptic, spasm-like movements occurring during sleep onset. However, their characteristics have yet to be defined. We conducted a clinicoelectroencephalographic study of children with RSS to clarify their detailed characteristics.To differentiate starts from epileptic spasms, we recruited children with brief "crescendo-decrescendo" muscle contractions that simultaneously involved the limbs and trunk without electroencephalogram changes, and that fulfilled the following criteria: (1) repeated occurrence (five or more) and (2) manifestation during sleep stage N1-N2. A total of nine children met these criteria. Their clinical information and video-electroencephalogram data were analyzed retrospectively.The background conditions observed at onset of RSS were perinatal hypoxic-ischemic encephalopathy (n = 4), West syndrome of unknown etiology (n = 1), and traumatic brain injury (n = 1). The age at onset of RSS, the number of starts in a given RSS cluster, the interval between starts, and the duration of surface electromyogram activity were between 3 and 46 months, 5 and 547,1 and 60 s, and 0.3 and 5.4 s, respectively. None of the median value of these parameters differed between children with and without corticospinal tract injury. During the median follow-up period of 33 months, RSS disappeared spontaneously in five.This is the largest case series of RSS clarifying their clinicoelectroencephalographic characteristics reported to date. To avoid unnecessary antiepileptic therapies, clinicians should be aware of RSS and distinguish it from other disorders involving involuntary movements or seizures, especially epileptic spasms.

Background Magnetic resonance imaging (MRI) abnormalities in preterm infants with bilirubin encephalopathy (BE) become less clear as the infants age. We assessed MRI findings in children with preterm BE older than 36 months corrected age (CA). Methods In a previous questionnaire survey, hospitals were asked to provide head MRI data of patients older than 36 months CA. MRI findings were reviewed by three pediatric neurology specialists and classified as no abnormalities, partial globus pallidus (GP) lesions, or diffuse GP lesions. Results In total, 33 MRI scans were available from 28 patients. The median gestational age and birth weight were 26 weeks and 824 g, respectively. The prevalence of MRI abnormalities was 100% in patients at 37 to 48 months CA, 71% in those at 49 to 60 months CA, 50% in those at 61 to 72 months CA, 67% in those at 73 to 84 months CA, and 38% in those at 85 months CA or older. Partial GP lesions were more common than diffuse GP lesions at all ages. No significant differences in sex, gestational age, birth weight, or gross motor function impairment were observed among lesion groups. Conclusions GP lesions were detected on MRI in most children with preterm BE when studied after 36 months CA, although MRI abnormalities became less apparent along with age. Partial GP lesions may be a characteristic of older children with preterm BE.

Background Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a common form of neonatal jaundice. Histopathological examination of the liver in patients with NICCD typically shows fatty liver, steatohepatitis, and liver fibrosis. Jaundice and fatty liver often improve by 1 year of age. We herein describe a girl who was diagnosed with NICCD based on an SLC25A13 mutation, although no fatty deposits were found on pathologic examination of the liver. Case presentation The patient in this case was a 3-month-old girl. At 2 months of age, she presented with jaundice, discolored stools, and poor weight gain and was found to have hyperbilirubinemia. Cholangiography revealed that she did not have biliary atresia. A laparoscopic liver biopsy was performed, and liver histopathology showed no fatty deposits. Genetic analysis revealed a compound heterozygous mutation in SLC25A13, and she was diagnosed with NICCD. She was given medium-chain triglyceride milk and gained weight. She resumed consumption of normal milk and breast milk, and her stool color improved. She was discharged at 4 months of age with adequate weight gain and a lower total bilirubin concentration. She was in good condition after discharge and showed normal development at the time of outpatient follow-up. Conclusions We experienced a case of NICCD in a patient without fatty liver. This case illustrates that the absence of hepatic steatosis in neonatal cholestasis does not rule out NICCD.

BackgroundAnaphylaxis is a severe systemic allergic reaction. Glucocorticoids rarely induce anaphylaxis. Determination of allergens includes the in vivo skin prick test (SPT) and intradermal skin test (IDST) and the in vitro basophil activation test (BAT). However, the usefulness of BAT in determining drug allergens has not been adequately studied.Case presentation A 10-year-old boy was admitted to our hospital because of fever and arthralgia for 2 weeks. He had not been treated with glucocorticoids. According to the laboratory tests and imaging studies, he was suspected to have bacterial myositis and was treated with ceftriaxone. However, his symptoms persisted for more than 2 weeks. With a suspicion of autoinflammatory arthritis, we planned methylprednisolone (mPSL) sodium succinate (MPS) during pulse therapy (30 mg/kg). Fifteen minutes after the injection of mPSL, he had wheezing and generalized wheal formation with decreased oxygenation. The administration of mPSL was discontinued because anaphylaxis was suspected. Thirty minutes after the administration of oxygen and oral olopatadine, the anaphylactic symptoms resolved. One month after discharge, SPT, IDST, and BAT were performed under the administration of oral prednisolone. The SPTs for MPS, hydrocortisone sodium succinate (HCS) and prednisolone sodium succinate (PSS) were negative. The IDST for MPS was positive. Moreover, the IDSTs for HCS and PSS were positive, whereas those for dexamethasone sodium phosphate and betamethasone sodium phosphate were negative. The BAT for MPS was negative at 1.0% and 1.9% after an incubation time of 1 hour and 24 hours, respectively, although the BAT for histamine as positive control was 60.4% and 18.3% after an incubation time of 1 hour and 24 hours, respectively. The BATs for HCS and PSS were negative. Therefore, we diagnosed as anaphylaxis secondary to the succinate ester in MPS.ConclusionsIn this case, IDST was useful for the diagnosis of MPS-induced anaphylaxis, whereas BAT was negative. This highlighted the need to choose the appropriate procedure in the diagnosis of steroid-induced anaphylaxis. The results in our patient suggested that BAT may be considered when IDST and SPT are negative. Further studies are necessary to clarify the diagnostic strategy for steroid-induced anaphylaxis.

Kawasaki disease (KD) is a febrile disease of childhood characterized by systemic vasculitis that can lead to coronary artery lesions (CAL). This was a prospective cohort study to determine the levels of the pentraxin 3 (PTX3), soluble CD24-Subtype (Presepsin) and N-terminal pro-brain natriuretic peptide (NT-pro BNP) in consecutive KD patients. From January 2013 to March 2015, all patients with KD admitted to Aichi Medical University Hospital who provided consent had their plasma saved before IVIG administration. In total, 97 cases were registered. 22 cases of incomplete KD were excluded from the outcome analysis. The total 75 cases were used for statistical analyses. A PTX3 threshold of >7.92 ng/ml provided a specificity of 88.5 %, a sensitivity of 94.4 %, and a likelihood ratio as high as 15.92 for the diagnosis of KD compared with febrile non-KD controls. Although an echocardiographic diagnosis of CAL in the early course of the disease was confirmed in 24 cases, it was not in the remaining 51 cases. Neither NT-proBNP nor Presepsin had statistical significance for the prediction of the echocardiographic CAL diagnosis. Only PTX3 was significantly predictive of the echocardiographic CAL diagnosis (p=0.01). The PTX3 level was significantly higher in the intravenous immunoglobulin (IVIG) non-responders (45.9±7.45) than in the IVIG responders (17.0 ± 1.46 ng/ml) (p< 0.001). The PTX3 level also correlated with the number of IVIG treatment courses needed to resolve fever (R² =0.64). Persistent CAL (pCAL) formation was observed in three cases; one of aneurysm only and two aneurysms with dilatations. The patients with pCAL had significantly higher PTX3 levels (85 ± 8.4 ng/ml) than patients without pCAL (22 ± 2.2 ng/ml) (p< 0.0001). In terms of pCAL prediction, the area under the curve (AUC) of receiver operating characteristic ROC curve of PTX3 was 0.99, and it was significantly greater than that of Presepsin (0.67) or NT-proBNP (0.75). PTX3 is a soluble pattern recognition molecule that acts as a main component of the innate immune system. These data suggest that PTX3 can be utilized as a definitive biomarker for the prediction of IVIG resistance and subsequent CAL formation in patients with KD.

ObjectiveWe examined the clinical manifestations of acute encephalopathy (AE) and identify risk factors for AE in children with tuberous sclerosis complex (TSC).MethodsThe clinical data of 11 children with clinically diagnosed TSC associated with AE and 109 children with clinically diagnosed TSC alone aged 4 years or older were collected from 13 hospitals.ResultsOf the 11 children with AE, 5 had histories of febrile seizures (FS), and all had histories of febrile status epilepticus (FSE). AE developed within 24 h after fever onset in all children with seizures lasting 30 min or longer. All children developed coma after seizure cessation. Head magnetic resonance imaging (MRI) revealed widespread abnormalities in the cerebral cortex, subcortical white matter, corpus callosum, basal ganglia, and thalamus. One child died; seven had severe neurological sequelae; and the other three, mild sequelae. Logistic regression analysis revealed that a history of FSE was correlated with the development of AE.SignificanceAE in children with TSC was characterized by sudden onset after fever, followed by coma, widespread brain edema evident on MRI, and poor outcomes. A history of FSE was a risk factor for the development of AE.

Brain MRI provides important information about suspected congenital CMV infection in neonatally underdiagnosed children. This study aimed to describe MRI findings in children in whom congenital CMV infection was not suspected during the neonatal period and was proven retrospectively.We enrolled 31 children referred to the pediatric neurology clinic with neurological symptoms who were proven to have congenital CMV infection based on dried umbilical cord samples. Upon diagnosis, MR and CT images were assessed using the van der Knaap scoring system integrated with additional variables. Two investigators independently assessed all images.The age at diagnosis was12 months in 14, 12-24 months in 11, and24 months in 6 patients. The initial symptom triggering clinic referral was delayed development in 22, seizure in 5, deafness in 3, and hemiplegia in 1 patient. Of the 31 children, 30 had a white matter (WM) abnormality predominant in the deep WM of the parietal lobe (n = 25). Anterior temporal lesions were observed in 21 children. Cortical lesions were observed in 7 children, suggestive of polymicrogyria. No child had cerebellar or brainstem abnormalities. Brain CT was performed in 22 of 31 children, and 11 showed punctate cerebral calcification in the periventricular and/or deep WM.Patients with congenital CMV infection with delayed neurological symptoms show a relatively uniform pattern of parietal-dominant multifocal WM lesions and anterior temporal lesions, with or without polymicrogyria.

Introduction: The aim of this study is to clarify bilirubin parameters and its treatment in preterm infants with bilirubin encephalopathy (pBE). Methods: We asked the responders to an earlier nationwide Japanese survey on pBE to provide additional information. pBE was diagnosed based on the criteria used in the nationwide survey. We collected data on serum total bilirubin (TB), direct bilirubin (DB), albumin, and unbound bilirubin (UB) levels during the first 8 weeks of life, and on phototherapy and exchange transfusion treatments. Results: We obtained clinical data from 75 patients with pBE from 58 hospitals (response rate of 59%), who were born between 2002 and 2016. The average peak TB level was 12.6 mg/dL (215 μmol/L), and the average age at peak attainment was 19.7 days after birth. Albumin level was Conclusions: Most patients with pBE lacked marked elevations in serum TB levels and the B/A ratio, the peaks of which were sometimes delayed to >4 weeks after birth.

Objective To summarize the neurophysiological properties of acute flaccid myelitis (AFM) and evaluate limb-based motor outcomes. Methods Nerve conduction studies (NCS) in 49 patients (21 females, 28 males; median age = 52 m) with AFM (median = 7 d after onset; range 1–122 d) were reviewed. Neurophysiological findings, together with treatment and prognosis, and neurophysiology–neuroimaging correlations were analyzed. Results The findings indicated that 64% of paralytic limbs during the acute stage (≤14 d after onset) showed diminished or absent compound muscle action potentials (CMAPs), 79% showed normal motor nerve conduction velocities, 55% showed decreased persistence or absent F-waves, and 95% showed normal sensory nerve conduction velocities. The rate of CMAP abnormalities increased from 41% on days 1–2 to 83% on days 13–14. The reduction in CMAP amplitude was correlated with weaker muscle strength at both the peak neurological deficit and the last follow-up. The baseline limb-based muscle strength at nadir and anterior horn-localized magnetic resonance imaging lesions at recovery stage (>14 d) were strong predictors of outcome at the last follow-up. Conclusions AFM typically shows neurophysiological features of neuronopathy. Significance NCS is probably useful in the diagnosis and evaluation of AFM.

Background: Carnitine plays an essential role in transfer of long-chain fatty acids to mitochondria for subsequent β-oxidation. No studies to date have characterized carnitine in children with KD. The objective of this study is to investigate the characteristics of serum free carnitine (FC) in hospitalized pediatric patients with Kawasaki disease (KD). Methods: In total, 45 patients with KD measured the levels of serum FC from October 2018 to December 2019 were analyzed retrospectively. We analyzed the clinical and laboratory parameters just before the Intravenous immunoglobulin (IVIG) including serum levels of serum FC with respect to the IVIG response. We also analyzed the relationship between serum FC and liver deviation enzymes or the duration of fever at diagnosis. Results: The median age was 33 months. IVIG was effective in 33 children (responders) and was ineffective in 12 (non-responders). The serum FC levels were higher in non-responders than in responders [(35.3 mmol/L (range, 26.8-118.4 mmol/L) vs. 31.4 mmol/L (range, 20.9-81.2 mmol/L), p value = 0.0496]. The FC levels before intravenous immunoglobulin (IVIG) in four-fifths of responders were below the normal range. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and FC were higher in non-responders than in responders. There were no different in patient characteristics and laboratory data according to fever duration at diagnosis. There was a correlation between FC and AST (R2=0.364, P=0.0015) and between FC and ALT (R2=0.423, P

Objective To assess the success rate, procedure time, and adverse events of intrathecal administration of nusinersen via the paramedian approach in adolescents and adults with spinal muscular atrophy (SMA) associated with scoliosis. Methods Seven patients with genetically confirmed SMA (age, 12–40 years) were included. Intrathecal administration of nusinersen was performed via paramedian approach using fluoroscopy after determination of the largest interlaminal foramen among L2-L3, L3-L4, or L4-L5 by three-dimensional computed tomography. We measured the times for preparation, positioning, and puncture, and the total time of stay. Adverse effects of intrathecal administration were noted. Results Intrathecal administration via paramedian approach was successful for all 38 opportunities. The median total time of stay was 44.0 min (interquartile range, 37.3–50.0 min). The total time of stay was significantly longer in patients with SMA type 1 than in those with SMA type 2, but was not different according to the severity of scoliosis. Adverse effects included oxygen supplementation, headache, and back pain. Sedation was correlated with oxygen supplementation and headache. Conclusions Intrathecal administration of nusinersen via the paramedian approach had the advantages of a high success rate and short procedure time with fewer adverse events in SMA patients associated with scoliosis.

This study was performed to evaluate the efficacy and tolerability of lacosamide (LCM) for paroxysmal kinesigenic dyskinesia (PKD) in children.We retrospectively reviewed the medical charts of pediatric PKD patients (aged16 years) treated with LCM. Data regarding demographic characteristics, proline-rich transmembrane protein 2 (PRRT2) gene variant, clinical features of PKD, dose of LCM, efficacy, and adverse events were recorded.Four eligible patients (3 males, 1 female) were identified, with an age of onset ranging from 8.3 to 14.7 years. PRRT2 variant was evaluated in three children and a c.649dupC variant was identified in one child with a positive family history. Attacks were bilateral in three children and left-sided in one. Two children had a family history of PKD and one child had a family history of benign infantile epilepsy. Treatment with carbamazepine failed in two children due to drowsiness and auditory disturbance. The initial dose of LCM was 50 mg/day in three children and 100 mg/day in one. All patients were attack-free within a few days. The maintenance dose was mostly similar to the initial dose. No adverse events related to LCM were reported during follow-up.LCM is an effective and well-tolerated treatment for PKD in children, and low-dose treatment may be viable.

Clinical identification of neonatal seizures (NS) remains challenging. The International League Against Epilepsy (ILAE) Task Force on Neonatal Seizures has proposed a new classification of NS, based on the 2017 ILAE seizure classification. One of the key points of this proposed NS classification is that seizure types should be determined by the "predominant" clinical feature. However, when the definition of "predominant" is uncertain, interobserver variability may arise.We asked 49 health professionals to classify 21 NS video-electroencephalogram (EEG) recordings using the proposed 9 seizure types.The degree of agreement among participants was low, and agreement was weak among experts in neonatal neurology. Among experts, the rate of agreement was50% for 2 NS. This disagreement was related to differences in the interpretation of "predominant features." Although interobserver variability was present among users of the new NS classification, the reproducibility of the NS classification was satisfactory.Education designed to foster consistent application of the standards for NS will be important for reducing interobserver variability and expanding the use of the new NS classification.

Neonatal epilepsies - neonatal seizures caused by remote symptomatic etiologies - are infrequent compared with those caused by acute symptomatic etiologies. The etiologies of neonatal epilepsies are classified into structural, genetic, and metabolic. Electroencephalography (EEG) and amplitude-integrated EEG (aEEG) are essential for the diagnosis and monitoring of neonatal epilepsies. Electroencephalography / aEEG findings may differ substantially among infants, even within infants with variants in a single gene. Unusual EEG/aEEG findings, such as downward seizure patterns on aEEG, can be found. Neonatal seizures are exclusively of focal onset. An International League Against Epilepsy task force proposed that the seizure type is typically determined by the predominant clinical feature and is classified into motor or non-motor presentations. Ictal EEG usually demonstrates a sudden, repetitive, evolving, and stereotyped activities with a minimum duration of 10 s. In epileptic spasms and myoclonic seizures, the cut-off point of 10 s cannot be applied. One must always be aware of electro-clinical dissociation in neonates suspected to have seizures. Amplitude-integrated EEG is also useful for the diagnosis and monitoring of neonatal epilepsies but aEEG cannot be recommended as the mainstay because of its relatively low sensitivity and specificity. At present, EEG findings are not pathognomonic, although some characteristic ictal or interictal EEG findings have been reported in several neonatal epilepsies. Deep learning will be expected to be introduced into EEG interpretation in near future. Objective EEG classification derived from deep learning may help to clarify EEG characteristics in some specific cases of neonatal epilepsy.

We report on a 4-year-old girl with a de novo GNAO1 mutation who had neurological findings, including decreased spontaneous movements, hypotonia, and dystonic features. She was referred to our hospital because of delayed psychomotor development. She showed hypotonia and decreased spontaneous movements. Voluntary movements of the limbs were more frequent in the lower extremities than in the upper extremities. Occasional dyskinetic features, such as awkward hand/foot posturing and grimacing, were seen during the voluntary movements. Serum metabolic screening, head magnetic resonance imaging, and electroencephalography were unremarkable. Whole-exome sequencing revealed a de novo mutation in the patient’s GNAO1 gene, c.709 G > A (p.E237K). We calculated the free-energy change using the FoldX Suite to evaluate the impact of the E237K mutation. The FoldX calculations showed an increased free-energy change in the active state of the GNAO1 protein, indicating that the E237K mutation destabilizes the active state complexes. No seizures, chorea, tremor, or myoclonia, which are frequently reported in patients with GNAO1 mutations, were observed as of the last follow up. Our patient will improve the understanding of early neurological features in patients with GNAO1 mutations.

We present here a late preterm infant with extensive brain lesions resulting from vitamin K deficiency. A female infant was born after 35 weeks of gestation by emergent cesarean section because of non-reassuring fetal status. Her mother had severe eating disorder and recurrent vomiting since early pregnancy. She was immediately intubated and ventilated because she was extremely pale, hypotonic, and non-reactive. Cerebral magnetic resonance imaging immediately after birth showed intraparenchymal hemorrhage in the left frontal lobe and cerebellum, marked cerebral edema, and cerebellar hypoplasia. Coagulation studies of the infant showed hepaplastin test

Background Immunomodulatory therapy has shown some therapeutic benefits in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. In this report, we describe the use of adrenocorticotropic hormone (ACTH) immunotherapy with good outcome in a patient with anti-NMDAR encephalitis. Subject and Methods A 4-year-old girl developed convulsions in her right arm and leg without impaired consciousness. These convulsions occurred frequently in clusters of 10–20 events of 10–20 s duration. She was admitted to our hospital on the 6th day following her initial series of convulsions. Flaccid paralysis of the right hand and leg was also found. Interictal electroencephalography showed high-amplitude slow waves. No abnormal findings were shown on MRI. 99mTc-ECD brain SPECT on the 14th day showed hyperperfusion in the left hemisphere, including the left basal ganglia. The convulsions ceased following the oral administration of valproic acid on the 10th day; however, paralysis associated with choreic dyskinesia of the right arm and leg remained. ACTH immunotherapy was then performed on the 15th day. We identified the presence of N-methyl-D-aspartate receptor antibody in CSF samples taken on the 6th day. After ACTH therapy, the patient fully recovered from the paralysis associated with choreic dyskinesia of the right arm and leg. She has not had a relapse and has not required medication for over a year. Conclusion ACTH immunotherapy may be a useful treatment option for patients with anti-NMDAR encephalitis, although further evaluation is required.

Background Rotavirus can, rarely, cause severe complications such as encephalopathy/encephalitis, myocarditis, sudden death, urinary stone, and gastrointestinal (GI) bleeding; and the incidence of these severe complications remains unclear. Additionally, it has not been determined whether rotavirus (RV) vaccine could reduce cases of severe complications or not. Methods A two-part questionnaire was designed to determine the number and clinical features of severe complications between 1 September 2008 and 31 August 2015, including the observation periods before and after RV vaccine introduction in Aichi Prefecture. Results Twenty-four cases of encephalitis/encephalopathy, eight cases of sudden death, three cases of urinary tract stone, and three cases of GI bleeding were reported during the 2008/2009 season and the 2012/2013 seasons. Although five cases of encephalitis/encephalopathy were reported, no other cases of severe complications were reported during the 2013/2014 and 2014/2015 seasons. No age difference was noted according to type of complication. Although onset of encephalitis/encephalopathy and of sudden death was around day 2 of illness, that of urinary tract stone and GI bleeding was slightly later (day 6 and day 4). In addition to the eight sudden deaths, fatal outcome was also noted in four cases (13.8%) of encephalitis/encephalopathy, and in one case of GI bleeding. Conclusion According to the questionnaire survey in Aichi Prefecture, the incidence of the four severe RV-associated complications appears to have declined as the vaccination rate has increased.

Background: Monocarboxylate transporter 8 (MCT8) deficiency is an X- chromosome-linked neurodevelopmental disorder resulting from impaired thyroid hormone transporter across cell membrane. The diagnosis of MCT8 deficiency is typically delayed owing to the late appearance of signs and symptoms as well as inability of standard biomarkers of neonatal screening to make an early diagnosis. Here, we report for the first time the ability to identify MCT8 deficiency at birth using dried blood spot (DBS) samples. Methods: We measured T3, T4, and reverse T3 (rT3) levels in DBS samples obtained at birth in healthy neonates (n = 42) and neonates with genetically confirmed diagnosis of MCT8 deficiency (n = 6). T3, rT3 and T4 levels were measured in 8 mm diameter DBS samples using liquid chromatography-tandem mass spectrometry. Results: Mean ± SD level of T3 tended to be higher in the MCT8 group than that in healthy neonates (0.941 ± 0.183 ng/mL vs. 0.742 ± 0.195 ng/mL, p = 0.0525). More importantly rT3 level in the MCT8 group was significantly lower than that in healthy neonates (0.317 ± 0.065 ng/mL vs. 0.768 ± 0.196 ng/mL, p < 0.0001) and the T3/rT3 ratio in the MCT8 group was significantly higher (3.04 ± 0.67 vs. 1.01 ± 0.34, p < 0.0001) with no overlap of values. T4 was lower in the MCT8 group than in healthy babies (93.4 ± 22.4 ng/mL vs. 156.7 ± 35.9 ng/mL, p < 0.0005) and the T3/T4 ratio of the MCT8 deficient group was higher (0.0105 ± 0.0029 vs. 0.0051 ± 0.0010, p< 0.0001). Conclusion: rT3 and T3/rT3 ratio measured in the DBS obtained from neonates can serve as biomarkers for diagnosis of MCT8 deficiency at birth.