The head circumference to chest circumference ratio provided an easy way to detect foetal growth restriction in term infants.

AIM: The head circumference to chest circumference (HC/CC) ratio has been used to identify low birth weight infants in developed countries. This study was conducted to examine whether the ratio could distinguish asymmetrical foetal growth restriction (FGR). METHODS: This retrospective observational study was conducted with 1955 infants (50.5% male) born at term between 2016 and 2020 at Tokyo Metropolitan Toshima Hospital, Japan. RESULTS: We found that 120 (6.1%) had FGR. Their mean birth weight was 3052.1 ± 367.3 g, and their mean gestational age was 39.1 ± 1.1 weeks. Logistic regression analysis showed that the association between the HC/CC ratio and FGR had a regression coefficient of -20.6 (p < 0.000). The linear regression analysis showed that the association between the HC/CC ratio and the birth weight z-score had a regression coefficient of -8.59 (p < 0.000). The coefficient of correlation was -0.33 (p < 0.001). The receiver operating characteristic curve for detecting FGR showed that the area under the curve was 0.75 and the cut-off value was 0.93, with sensitivity of 75.8% and specificity of 60.8%. CONCLUSION: Our study established the associations between HC/CC ratio and FGR and birth weight z-scores and confirmed that the ratio provided an easy way to detect FGR in term-born infants.

Urinary angiotensinogen in pediatric urinary tract infection.

BACKGROUND: Urinary tract infection (UTI) is one of the most common diseases in children, and urinary angiotensinogen (U-AGT) is a new biomarker gathering attention in many renal diseases. U-AGT reflects intrarenal renin-angiotensin system (RAS) activity. We conducted a study to measure U-AGT in children <4 months old with UTI. METHODS: All children <4 months old who came to Toshima Hospital with fever between January 2015 and December 2015 were included. Patients were divided into a UTI group and a non-UTI group, and U-AGT was measured. RESULTS: Median U-AGT was higher in patients with UTI compared with patients without UTI: (0.56 ng/dL, range, 0.025-2.753 ng/dL vs 0.13 ng/dL, range, 0.008-1.697 ng/dL, respectively; P < 0.05). CONCLUSIONS: U-AGT is elevated in UTI patients, and RAS activation may contribute to renal injury caused by UTI.

Clinical Features of RS Virus Infection before, during, and after COVID-19 Pandemic.

The COVID-19 pandemic has impacted the epidemiology of other infectious diseases. In particular, the respiratory syncytial (RS) virus infects almost all children during their first or second year of life. However, during the COVID-19 pandemic, many restrictions were enforced that isolated children from other children. Therefore, we hypothesized that the clinical features of RS virus infection were altered and conducted a study to evaluate these changes. This observational study included children below the age of six years who were admitted to the Tokyo Metropolitan Toshima Hospital. Their clinicodemographic data were extracted from medical records. The 369 children eligible for the study were assigned to three groups: "pre-pandemic" (group 1, n = 253); "during pandemic" (group 2, n = 77), and "post-pandemic" (group 3, n = 39). Logistic regression analysis revealed that compared to group 1, the odds ratio (OR) for oxygen use was significantly higher in groups 2 (OR 1.85. 95% confidence interval [CI] 1.06-3.23; p < 0.05) and 3 (OR 3.36, 95% CI 1.59-7.12; p < 0.01), and the use of mechanical ventilation was significantly higher in group 3 (OR 4.89, 95% CI 1.71-13.94; p < 0.01). This study highlights changes in the clinical features of RS virus infection during and after the COVID-19 pandemic.

High number of seizures and unconsciousness in patients with SARS-CoV-2 omicron variants: a retrospective study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variants are now a pandemic. There are differences in clinical features in SARS-CoV-2 variants and we conducted this study to assess the clinical features of coronavirus disease (COVID-19) in children with SARS-CoV-2 omicron variants. The study included children with COVID-19 arrivedto Tokyo Metropolitan Toshima Hospital between January 2020 and October 2022. The clinical features of 214 children with SARS-CoV-2 non-omicron variants and 557 children with omicron variants were compared. In the SARS-CoV-2 omicron variant group, more patients had fever, sore throat, nausea and/or vomiting, and seizures and/or disorders of consciousness. In SARS-CoV-2 non-omicron variants, there was only one patient with seizure and/or unconsciousness whereas there were 92 children in omicron variants. Among these 92 patients, 46 (49%) were diagnosed with simple febrile seizures; 23 (25%), with complex febrile seizures; 10 (11%) with status epilepticus; and two (2%) with encephalopathy. Their mean age was 4.0 ± 3.0 years-a wider age distribution than that in other febrile seizures but similar to that in febrile seizures in patients with influenza. SARS-CoV-2 omicron variants are likely to cause seizures and unconsciousness in children and their age distribution was wider than other febrile seizures patients but similar to those in influenza patients. In clinical practice in patients with COVID-19 and influenza, clinicians should be aware of these features.

Evaluation of the transmission of SARS-CoV-2 through breast milk: a case series.

Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through breast milk remains controversial. This study aimed to determine the presence of SARS-CoV-2 in breast milk and assess its transmissibility to the child in infancy. Eleven samples were obtained from nine mothers with coronavirus disease 2019 (COVID-19). All but one sample had negative results on a reverse transcription-quantitative polymerase chain reaction. Among nine children, five were diagnosed with COVID-19, including one child whose mother's milk tested positive. Although SARS-CoV-2 RNA was detected in breast milk, its possible transmission via breastfeeding could not be established. Thus, we conclude that the physical attachment between mother and child is a conceivable transmission route.

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

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

Case report: Mild encephalitis with a reversible splenial lesion associated with SARS-CoV-2 infection in a patient with MYRF variant.

We report a 14-year-old girl with a heterozygous p. Gln403Arg variant in the MYRF gene, who had five episodes of encephalopathy. She experienced reduced consciousness, numbness in the arm, and impaired verbal communication from day 4 of SARS-CoV-2 infection. Magnetic resonance imaging of her head showed reduced water diffusion in the corpus callosum and deep white matter. These features were similar to those seen in her previous episodes of encephalopathy. She was treated with methylprednisolone pulse therapy and recovered completely within a week.

A COL4A1 variant in a neonate with multiple intracranial hemorrhages and congenital cataracts.

A 2-day-old neonate presented with seizures, multiple intracranial hemorrhages, and bilateral congenital cataracts. Targeted next-generation sequencing of the collagen type IV alpha 1 chain (COL4A1) gene revealed a heterozygous de novo missense variant (NM_001845.6:c.2291G>A/p.Gly764Asp). This missense variant adds to the compendium of COL4A1 variants and is associated with a COL4A1-related disorder.

Clinical Features of Children with COVID-19 in Initial Time of Pandemic.

Objectives: COVID-19 (Coronavirus Disease 2019) is now a global pandemic. Although children are said to have mild symptom, their clinical features are not known well. We conducted a retrospective study during initial term of pandemic to understand the difference of clinical features including clinical symptoms and patients' characteristics of COVID-19 children and those without COVID-19. Materials: To compare clinical features between children with and without COVID-19, we collected data on children who received a COVID-19 test between March 25th and October 31st, 2020. All data were collected from medical records. Methods: There were three groups of patients in the study sample; patients with COVID-19, patients with close COVID-19 contact and performed COVID-19 tests, and patients suspected COVID-19 but tested negative. We analyzed the clinical features of the groups. Results: A total of 108 patients were included in this study, of whom 30 were patients with COVID-19, 25 were patients with close COVID-19 contact, 51 were suspected COVID-19 but tested negative, and two were excluded because they were infants born from COVID-19 mothers. The statistical analysis showed that children with COVID-19 had contact with COVID-19 patients had fewer clinical symptoms including cough and fever compared to children with a negative test of COVID-19. Sensitivity analysis showed that fever, cough, fever and/or cough could not distinguish children with COVID-19 from those without COVID-19. As conclusion, children with COVID-19 have less symptoms as fever or cough and the clinical symptoms cannot distinguish them from children with other diseases.

Effects of early enteral feeding on fecal elastase 1 and plasma secretin.

BACKGROUND: Enteral feeding is known to be effective on the development of gut hormone secretion and pancreatic exocrine function. The aim of the present study was to examine the effects of extremely early enteral feedings on the development in very low-birthweight (VLBW) infants. METHODS: Fecal elastase 1 and plasma secretin concentrations were measured at four different periods during the first 28 days of life in VLBW infants, with extremely early enteral feeding starting within 24 h of birth, as well as in control infants. RESULTS: Fecal concentrations of elastase 1 at 7, 14 and 28 days after birth were significantly higher than those at 1 or 2 days in both the early feeding and control groups. Fecal elastase 1 levels in the early feeding group were significantly higher than those in the control group at 7 and 14 days after birth. The plasma concentration of secretin at 14 days after birth was significantly higher than that at 1 or 2 days and 7 days after birth in the early feeding group. No significant differences in plasma secretin levels were detected between the early feeding and control groups at 1 or 2 days, 7 days and 28 days after birth, but a significant difference in secretin level was observed between the two groups at 14 days after birth. CONCLUSIONS: Extremely early enteral feedings may play an important role in the development of pancreatic exocrine function and secretin secretion in the early period of life in VLBW infants.

Potential-modulated electrochemiluminescence of a tris(2,2'-bipyridine)ruthenium(II) / lidocaine system under 430 kHz ultrasound irradiation.

The electrochemiluminescence (ECL) of tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)32+) in the presence of lidocaine was investigated under ultrasound (US) irradiation. The sonoelectrochemical experiments are conducted by indirect irradiation of ultrasound with a piezoelectric transducer operating at 430 kHz. In a supporting electrolyte at pH 11, the Ru(bpy)32+/lidocaine system gave weak ECL peaks around +1.2 V and +1.45 V, respectively. The ECL signal at +1.2 V was attributed to redox reactions of the oxidative intermediates of Ru(bpy)32+ and lidocaine, while the signal at +1.45 V was assumed to be caused by an advanced oxidation process due to the generation of hydroxyl radicals (OH) at the electrode surface. In this study, the potential modulation approach is employed in the study of ECL process upon US irradiations because it can suppress the noise components from sonoluminescence effectly and improve the resolution of ECL-potential profiles. It is found ECL signals were greatly enhanced upon US irradiation at the output power of 30 W, however, the relative intensity of ECL signal at +1.2 V was larger than that obtained with a rotating disk electrode even though the mass transport effect is equilvalent. The experiment results suggest that the chemical effect (i.e., generation of OH) by 430 kHz US becomes remarkable in the electrochemical process. Detailed ECL reaction routes under US are proposed in this study.

Depressive tendency in children with growth hormone deficiency.

AIM: This study assessed changes in depressive tendency of children with growth hormone deficiency. METHODS: The 41 children with growth hormone deficiency were assessed using the Depression Self-Rating Scale for Children. A score of 16 or more indicated a depressive tendency. The first assessment was carried out before growth hormone treatment, and the second one was carried out at 6 months or longer after the beginning of growth hormone treatment. RESULTS: The Depression Self-Rating Scale for Children improved significantly from 9.7 +/- 6.1 points before treatment to 6.9 +/- 4.6 points after treatment (P= 0.0013). A depressive tendency was observed in six patients (15%) before growth hormone treatment, and in two patients (5%) after treatment. No significant relationship was observed between the decrease in the score and the length of the treatment. A significant improvement was observed for 6 of the 18 items in the Depression Self-Rating Scale for Children. CONCLUSION: A depressive tendency was relatively common in children with growth hormone deficiency, and the Depression Self-Rating Scale for Children was decreased after growth hormone treatment. These results suggest that growth hormone treatment may have positive effects on the psychosocial aspects in children with growth hormone deficiency.

Sepsis associated encephalopathy in an infant with biliary atresia.

We describe a girl with sepsis-associated encephalopathy complicating biliary atresia. At 4 months of age, decreased consciousness and repetitive seizures of the left upper and lower extremities occurred in association with fever. Pseudomonas aeruginosa was cultured from blood, while bacterial culture was negative and cell counts were normal in cerebrospinal fluid. The interleukin-6 level in the cerebrospinal fluid was markedly elevated. MRI revealed unilateral subcortical white matter lesions in the right hemisphere. She was diagnosed as having sepsis-associated encephalopathy and was treated with dexamethasone and midazolam. She achieved normal psychomotor development until the last follow-up at 19 months of age, whereas mild atrophic changes were observed in the right hemisphere.

An episode of acute encephalopathy with biphasic seizures and late reduced diffusion followed by hemiplegia and intractable epilepsy observed in a patient with a novel frameshift mutation in HNRNPU.

Microdeletions in the 1q44 region encompassing the HNRNPU gene have been associated with infantile spasms and hemiconvulsion-hemiplegia-epilepsy syndrome. Recent studies have revealed that heterozygous HNRNPU variants resulted in early onset epilepsy and severe intellectual disability. A de novo frameshift mutation in HNRNPU was identified in a 5-year-old boy with developmental delay associated with Rett-like features including stereotypic hand movements and respiratory abnormalities with episode of apnea and hyperpnea followed by falling. He also showed an episode of acute encephalopathy with biphasic seizures and late reduced diffusion followed by hemiplegia and intractable epilepsy. Unique and variable clinical features are related to loss-of-function or haploinsufficiency of HNRNPU.

Reconsideration of the diagnosis and treatment of childhood migraine: A practical review of clinical experiences.

OBJECTIVE: To provide insight into the wide spectrum of migraine during childhood to establish practical and comprehensive treatment strategies. BACKGROUND: Although recent studies have confirmed the effect of anti-migraine agents in childhood headaches fulfilling the criteria of migraine without aura, there have been no studies regarding the efficacy of these drugs in childhood migraine without aura not filling the diagnostic criteria. METHODS: In total, 154 patients with a clinical diagnosis of migraine, with onset of repetitive headaches at the age of ⩽15years, were retrospectively included from clinics in seven tertiary medical centers. RESULTS: Patients' diagnoses included migraine with aura (n=49), migraine without aura (n=65), clinical migraine without aura not fulfilling International Classification of Headache Disorders-3 beta criteria (suspected migraine without aura; n=38), and hemiplegic migraine (n=2). Abortive medicine was effective in 74 of 97 patients, and preventive medicine was effective in 61 of 84 patients. Drugs with high efficacy were acetaminophen and ibuprofen for abortive therapy and cyproheptadine, amitriptyline, and propranolol for preventive therapy. Psychosocial problems were less common, and abnormalities on electroencephalography were more common in the suspected migraine without aura group. Otherwise, clinical features and drug responsibility were comparable among the migraine with aura, migraine without aura, and suspected migraine without aura groups. Retrospectively, experts clinically diagnosed childhood migraine without aura when the headache met at least one of the three criteria B, C, and D in International Classification of Headache Disorders-3 beta in addition to A and E. Abortive and preventive medication including paroxetine (n=2) benefited 10 and 15 of the 33 patients with daily headache, respectively. Psychotherapy/counseling (n=4), treatment for orthostatic dysregulation (n=4), and elimination of stressors (n=3) markedly alleviated headache in this group. CONCLUSION: Our results indicated that those with suspected migraine without aura not filling International Classification of Headache Disorders diagnostic criteria should be included in the treatment for migraine. Treatment should also be targeted to comorbid developmental disorders, orthostatic dysregulation, and psychosocial problems in patients with refractory daily headaches.

Congenital muscular dystrophy with glycosylation defects of alpha-dystroglycan in Japan.

Glycosylation defects of alpha-dystroglycan (alpha-DG) cause various muscular dystrophies. We performed clinical, pathological and genetic analyses of 62 Japanese patients with congenital muscular dystrophy, whose skeletal muscle showed deficiency of glycosylated form of alpha-DG. We found, the first Japanese patient with congenital muscular dystrophy 1C with a novel compound heterozygous mutation in the fukutin-related protein gene. Fukuyama-type congenital muscular dystrophy was genetically confirmed in 54 of 62 patients. Two patients with muscle-eye-brain disease and one Walker-Warburg syndrome were also genetically confirmed. Four patients had no mutation in any known genes associated with glycosylation of alpha-DG. Interestingly, the molecular mass of alpha-DG in the skeletal muscle was similar and was reduced to approximately 90 kDa among these patients, even though the causative gene and the clinico-pathological severity were different. This result suggests that other factors can modify clinical features of the patients with glycosylation defects of alpha-DG.

Amplitude-integrated EEG revealed nonconvulsive status epilepticus in children with non-accidental head injury.

OBJECTIVE: We describe the clinical course and amplitude-integrated EEG findings in three children with non-accidental head injury and discuss on the importance of continuous aEEG monitoring in infants. METHODS: NCSE was defined as a continuous 30-min seizure or briefer seizures occurring consecutively comprising at least 30 min of any 1-h period. Non-accidental head injury was diagnosed on the basis of neuroimaging findings such as subdural hemorrhage. Antiepileptic treatment was performed with continuous amplitude-integrated EEG monitoring. RESULTS: The age of the patients ranged from 48 days to nine months. All of them had loss of consciousness and seizures on presentation. Nonconvulsive status epilepticus without clinical symptoms were recognized in all patients. Vigorous antiepileptic treatment against nonconvulsive status epilepticus was made in two patients, whereas nonconvulsive status epilepticus disappeared within one hour without additional treatment in one. CONCLUSIONS: Our experience indicates that nonconvulsive status epilepticus were not uncommon in children with non-accidental head injury. Continuous amplitude-integrated EEG monitoring will be one of the useful methods in encephalopathic children in order to estimate seizure burden objectively and to treat seizures appropriately.

A boy with a severe phenotype of succinic semialdehyde dehydrogenase deficiency.

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder affecting γ-aminobutyric acid degradation. We describe here a boy with a severe phenotype of SSADH deficiency. He was referred because of a developmental delay at 4 months of age. At the age of 8 months, severe seizures developed. The diagnosis of SSADH deficiency was confirmed by an increase in 4-hydroxybutyric acid and heteroallelic mutation in the ALDH5A1 gene. His seizures were successfully treated with high-dose phenobarbital, and the electroencephalogram (EEG) abnormalities were ameliorated. However, the patient showed a degenerative clinical course with severe neurological deficits. A magnetic resonance imaging (MRI) scan revealed abnormal high intensities in the putamina and caudate nuclei on T2-weighted images, followed by marked atrophic changes. The clinical manifestation of our patient indicates the wide variety of SSADH deficiency phenotypes.

Acute encephalopathy with biphasic seizures and late reduced diffusion associated with hemophagocytic syndrome.

We reported a girl with HHV-6 infection associated with both acute encephalopathy with biphasic seizures and late reduced diffusion, and hemophagocytic syndrome. She had a prolonged convulsion after a one-day history of febrile illness. Cerebrospinal fluid or brain CT showed no abnormalities on admission and her consciousness was recovered on the next day. However, a prolonged seizure and deterioration of consciousness appeared on the sixth day of illness. Diffusion-weighted images revealed marked reduction of water diffusion in the bilateral frontal areas. HHV-6 infection was virologically proven by polymerase chain reaction. She was treated with gamma-globulin, steroid pulse therapy, and brain hypothermia. In addition, decrease in white blood cells and platelet counts, and elevation of liver enzymes and ferritin were noted on the fourth day of illness. Hemophagocytic macrophages were revealed by bone marrow aspiration on the sixth day. Her hematological and blood chemistry abnormalities recovered gradually after steroid pulse therapy. An elevation of interleukin-6, -8, and -10, and tumor necrosis factor in the serum and that of interleukin-4, -6, and-8 in the cerebrospinal fluid were observed at the onset of a late seizure. These facts suggested that hypercytokinemia will be related to the pathogenesis of acute encephalopathy of our patient.