Maternal fermented food intake and infant neurodevelopment: The Japan Environment and Children's Study.

BACKGROUND AND OBJECTIVES: Fermented foods play an important role in establishing intestinal bacterial flora, and the composition of the intestinal bacterial flora might be associated with neurodevelopment. This study investigated the association between maternal intake of fermented foods during pregnancy and early neuro-development in offspring. METHODS AND STUDY DESIGN: Data were analyzed for 73,522 pregnant women participating in the Japan Environment and Children's Study. Their intake of four common fermented foods during pregnancy was assessed using a semi-quantitative FFQ. Neurodevelopment in their infants at 1 year of age was estimated using the Ages and Stages Questionnaires. RESULTS: Multivariable logistic regression analysis showed that maternal intake of miso soup and fermented soybeans was each associated with a significantly reduced risk of delay in infant communication skills. Maternal intake of fermented soybeans and cheese was each associated with a significantly reduced risk of delay in fine motor skills in the third and fourth quartiles. For problem-solving, preventive associations were observed with maternal intake of fermented soybeans in the second and third quartiles and with maternal intake of cheese in the third and fourth quartiles. Maternal intake of yogurt was associated with a significantly reduced risk of delay in personal-social skills in the third and fourth quartiles, while that of cheese was associated with a reduced risk in the third quartile. No reductions in risk were observed for gross motor skills. CONCLUSIONS: Our results suggest that fermented food intake during pregnancy may have beneficial associations with several areas of psychomotor development in children.

Clinical and electroencephalographic findings prior to the onset of juvenile myoclonic epilepsy: A case series.

The purpose of this study was to investigate the timing of generalized electroencephalographic abnormalities in patients with juvenile myoclonic epilepsy who were followed up long term before the onset of juvenile myoclonic epilepsy. We enrolled juvenile myoclonic epilepsy patients whose course of epilepsy had been observed for >5 years before the onset of juvenile myoclonic epilepsy, those who had undergone electroencephalogram recording more than twice before the onset of juvenile myoclonic epilepsy, and those who had terminated antiseizure medications for at least 2 years before the onset of juvenile myoclonic epilepsy. Patients who had transitioned from childhood absence epilepsy to juvenile myoclonic epilepsy were excluded. We retrospectively reviewed the medical records and neurophysiological data of the patients. Four patients met the inclusion criteria. One patient was diagnosed with febrile seizures during childhood, and the remaining three had transitioned to juvenile myoclonic epilepsy from other epileptic disorders, such as self-limited epilepsy with autonomic seizures, genetic epilepsy with febrile seizure plus, or nonspecific genetic generalized epilepsy. All patients exhibited generalized spike-wave discharges or photoparoxysmal responses for >2 years before the onset of juvenile myoclonic epilepsy. The four patients had transitioned to juvenile myoclonic epilepsy from other epileptological preconditions. Patients with juvenile myoclonic epilepsy may show generalized electroencephalographic abnormality many years prior to the onset of symptoms. Generalized spike-waves on the electroencephalogram during the course of any type of epilepsy or febrile seizure may be a risk factor for developing juvenile myoclonic epilepsy.

Recurrence rates and risk factors for seizure recurrence following antiseizure medication withdrawal in adolescent patients with genetic generalized epilepsy.

OBJECTIVE: This study aimed to identify the recurrence rate of genetic generalized epilepsy (GGE) and risk factors for recurrence after antiseizure medication (ASM) withdrawal in adolescent patients. METHODS: We retrospectively reviewed medical records of patients with GGE who were included in the registry at the Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital from 2000 through 2020. The eligibility criteria were as follows: onset of epileptic seizures at <15 years of age, treatment with an ASM, and attempted treatment withdrawal at 10-19 years of age. The rates of seizure recurrence after drug withdrawal were evaluated. Moreover, several variables were evaluated as predictors of recurrence. RESULTS: In total, 77 patients with GGE (21, 13, and 43 patients with juvenile myoclonic epilepsy [JME], juvenile absence epilepsy [JAE], and epilepsy with generalized tonic-clonic seizures alone [EGTCSA], respectively) were included in this study. Recurrence was detected in 68% of patients with GGE (86%, 31%, and 70% of patients with JME, JAE, and EGTCSA, respectively). Recurrence rates for patients who developed epilepsy at ≥13 years of age, those who started dose reduction at ≥16 years of age, those who exhibited a seizure-free period of <36 months before withdrawal, and those who chose to discontinue treatment at their own discretion were significantly higher than those for their counterparts. Multivariate analysis revealed that initiation of dose reduction at ≥16 years of age was associated with increased recurrence risk. Meanwhile, a diagnosis of JAE was associated with decreased recurrence risk. All patients with JAE were treated with valproic acid. SIGNIFICANCE: Antiseizure medication withdrawal at ≥16 years of age and a diagnosis other than JAE may be independent risk factors for seizure recurrence after drug withdrawal in adolescent patients.

Polymicrogyria with calcification in Pallister-Killian syndrome detected by microarray analysis.

BACKGROUND: Pallister-Killian syndrome (PKS) is a rare disorder caused by the mosaic tetrasomy of chromosome 12p, and is characterized by facial dysmorphism, developmental delay, hypotonia and seizures. RESULTS: We report a patient with PKS showing unique polymicrogyria with calcification. He had delayed development and dysmorphic facial features including frontal bossing, hypertelorism, and high arched palate at 6 months of age. Neuroimaging revealed unilateral polymicrogyria with spot calcifications, which predominantly affected the right perisylvian region. Chromosome G-banding showed the karyotype 46,XY, however, array-based comparative genomic hybridization analysis showed mosaic duplication of chromosome 12p, in which CCND2, which encodes cyclin D2 and is a downstream mediator of PI3K-AKT pathway, is located. Supernumerary chromosome of 12p was detected in 58% of buccal mucosa cells by the interphase fluorescence in situ hybridization analysis using chromosome 12 centromere-specific D12Z3 probe. The diagnosis of PKS was made based on distinctive clinical features of our patient and the results of cytogenetic analyses. CONCLUSION: This report is, to our knowledge, the first case of a patient with PKS who clearly demonstrates polymicrogyria colocalized with calcifications, as shown by CT scans and MRI, and suggests that a patient with PKS could show structural brain anomalies with calcification. We assume that somatic mosaicism of tetrasomy could cause asymmetrical polymicrogyria in our patient, and speculate that increased dosages of CCND2 at chromosome 12p might be involved in the abnormal neuronal migration in PKS.

Neurodevelopmental outcomes at 3 years for infants with congenital heart disease and very-low birthweight.

BACKGROUND: Both congenital heart disease (CHD) and very-low birthweight (VLBW) infants are at a very high risk of neurodevelopmental delay. We investigated neurological development at 3 years in pediatric patients with CHD after surgical intervention, those of VLBW, and healthy controls. METHODS: We enrolled pediatric patients with CHD (n = 67), VLBW (n = 67), and healthy controls (n = 81). Infants with CHD were grouped into those with single ventricle and two ventricles, and infants with VLBW were grouped into those with birthweights of <1000 and 1000-1499 g. Neurodevelopmental outcomes at 3 years were evaluated using the Bayley Scales of Infant and Toddler Development, Third Edition. RESULTS: Compared with healthy controls, a significant deficit in the language, cognition, and motor skills scores were observed in infants with CHD and VLBW. Infants with a single ventricle exhibited significantly low scores in language and gross motor skills. No statistically significant difference was observed between the birthweight groups of <1000 and 1000-1499 g. CONCLUSION: Neurodevelopmental outcomes for infants with both CHD and VLBW showed impairment. Notably, neurodevelopmental delays in infants with a single ventricle were remarkable. Thus, because infants with both CHD and VLBW are at high risk of neurodevelopmental disorders, periodic developmental screenings and support are warranted for these children.

Brain Development of Children With Single Ventricle Physiology or Transposition of the Great Arteries: A Longitudinal Observation Study.

To define the correlation between neuroanatomic and developmental outcomes of children with single ventricle (SV) or transposition of the great arteries (TGA), a prospective longitudinal study was performed in preschool and school-age children. Twenty-seven children with congenital heart disease (9, TGA; 18, SV) were included. Participants underwent 3-dimensional magnetic resonance imaging (MRI) and neurodevelopmental assessment at around 3 years (preschool age) and at 9 years (school age), and 48 healthy controls underwent MRI, and their data were used to derive best-fit models for normal brain volumes for comparisons with congenital heart disease patients. Total brain volume (TBV) and regional brain volumes remained significantly smaller in SV children than in TGA children at both time points, though the growth slope of TBV was not significantly different between the SV and TGA groups. Although the psychomotor developmental index at preschool was significantly lower in SV patients, the full-scale IQ at school age was not significantly lower in SV patients. There was a strong correlation between full-scale IQ and TBV (r = 0.49, P = 0.005). Despite the current best practices, persistently lower TBV was seen in SV patients until 9 years of age. For both the SV and TGA groups, TBV at 3 years was a strong predictor of TBV at 9 years. Since there was a correlation between TBV and IQ at 9 years, identification of factors that affect brain growth until 3 years will be imperative to improve patients' cognitive function at school age.

Toddler Neurodevelopmental Outcomes Are Associated With School-Age IQ in Children With Single Ventricle Physiology.

To examine whether neurodevelopment at preschool age predicts IQ levels and needs for special education services in school-age children with single ventricle (SV) physiology. Thirty-five patients with SV physiology were assessed using the Bayley Scale of Infant and Toddler Development (BSID) II or III at 3 years and the Wechsler Intelligence Scale for Children-Fourth Edition (WISC) at 8 years. Whether the children were receiving special education services was also determined. Factors associated with the mental developmental index (MDI) of the BSID, the full-scale IQ (FSIQ) of the WISC, and special education services were also analyzed. The MDI and FSIQ of children with SV physiology were significantly lower than the values in healthy children (P < 0.01). The MDI at 3 years was moderately correlated with FSIQ at 8 years (P < 0.01, R2 = 0.41). Ten patients (28.6%) received special education services in their school. Children with MDI <85 were more likely than those with MDI ≥85 to require special education services at school age (53% and 10%, respectively, P < 0.01). Weight at birth and stage II were correlated with the MDI, extracorporeal circulation time at stage II was correlated with FSIQ, and age at Fontan operation was correlated with FSIQ and special education services. The toddler neurodevelopment index may predict not only IQ levels but also the need for special education services in school-age children. Children with low neurodevelopmental scores need to be followed closely for a long time.

Clinical Factors That Affect the Relationship between Head Circumference and Brain Volume in Very-Low-Birth-Weight Infants.

BACKGROUND AND PURPOSE: Measuring head circumference (HC) in infants is an easy screening procedure with which to detect abnormalities in brain growth. It has been demonstrated that HC can predict total brain volume (TBV) in very-low-birth-weight (VLBW) infants. However, the correlation between HC and TBV was weaker than that observed in healthy term-born toddlers, suggesting that there are factors that influence the relationship between HC and TBV. The aim of this study was to identify the clinical risk factors that caused a deviation from the regression line obtained between HC and TBV. METHODS: The study population was based on 37 VLBW infants, who underwent a clinical magnetic resonance imaging (MRI) examination at a term-equivalent age, during 2013-2015, at Toyama University Hospital. The HC and the TBV were both adjusted for sex, multiple births, and postmenstrual age. The relationship between TBV/HC and clinical characteristics was evaluated. RESULTS: There was a positive correlation between HC and TBV (r = .58, P = .000168). Two clinical factors, the lower birth body weight (BBW) (r = .38, P = .02) and dolichocephaly (r = 0.46, P = .006), were identified as factors that negatively affected the TBV/HC ratio. After excluding infants with low BBW or with dolichocephaly, the correlation between HC and TBV was higher (r = .63). CONCLUSIONS: Although HC has predictive value for TBV in VLBW infants, care should be taken in infants with low BBW (BBW less than 600 g) or dolichocephaly (MRI-based cranial index less than .68), which were related to overestimation of TBV.

[Complete response in an elderly patient with advanced gastric scirrhous cancer treated with combined chemotherapy of TS-1 and CDDP].

A 79-year-old male was diagnosed as having a scirrhous cancer of the stomach. Carcinomatous peritonitis was suspected on abdominal CT examination and the CA19-9 showed a high level of 95 U/ml. The patient was treated with combined chemotherapy of TS-1 and CDDP. TS-1 (100 mg/day) was administered for 14 days followed by 14 days rest as one course. CDDP was administered in 24-h continuous intravenous infusion on day 8. This treatment was done every 4 weeks regularly. After 5 courses, X-ray and endoscopy examinations revealed disappearance of cancerous lesions in the stomach with an improvement in the extensibility. No cancer cell were confirmed by endoscopic biopsy, nor did a CT-scan detect carcinomatous peritonitis. The CA19-9 decreased within the normal limit. Ten months after chemotherapy was started, the patient was very healthy without a recurrence of cancer. This combined chemotherapy has administered in 8 courses, and during this period no high grade toxicities (WHO grade 3 or 4) occurred. This TS-1/CDDP chemotherapy was effective for scirrhous gastric cancer and might be administered safely even for aged patients.

[Complete response in a case of simultaneous esophageal and gastric cancer treated by combined radiotherapy and chemotherapy of TS-1 and CDDP].

A 75-year-old male patient was hospitalized for examination of abdominal trouble. Endoscopic examination simultaneously revealed 0-I pl + II c esophageal cancer and type 3 gastric cancer. Endoscopic treatment is impossible to resect the lesion completely. It is difficult for the patient to undergo an operation because he has suffered from a cardiac infarction and pulmonary trouble. Thus, gastric cancer was treated by chemotherapy and esophageal cancer by concurrent chemoradiotherapy with chemotherapy used for gastric cancer. Chemotherapy consisted of CDDP and TS-1 every 4 weeks. TS-1 (100 mg/day) was administered on days 1 to 21, and CDDP (70 mg/m2) was infused for 24 hours on day 8. Radiotherapy (5 days/week) at 2 Gy/day was concurrently started from the beginning of chemotherapy. At day 8 in the 2nd course of chemotherapy, leucocytopenia of grade 2 and appetite loss of grade 3 (NCI-CTC) were seen. Chemoradiotherapy was then suspended for one week. After recovery from toxicity, treatment was continued for a week. A total of 64 Gy was administered. After treatment, endoscopic examination with biopsy revealed the disappearance of gastric and esophageal cancer.