Infant with right hemiplegia due to acute encephalopathy with biphasic seizures and late reduced diffusion (AESD): A case report.

RATIONALE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a condition characterized by biphasic convulsions and disturbance of consciousness. In Japan, the most common pediatric cases of acute encephalopathy are associated with infection. AESD usually occurs in early childhood, with the characteristic magnetic resonance imaging (MRI) appearance called "bright tree appearance." The disease often has neurological sequelae and interferes with the schooling of children and their activities of daily living; however, there are few clinical case reports of hemiplegia caused by AESD. PATIENT CONCERNS: A case with right-sided hemiplegia due to AESD in an 11-month-old girl who was followed up to 30 mo of age. DIAGNOSES: The patient was diagnosed with overlap AESD and hemiconvulsion-hemiplegia-epilepsy syndrome (HHE syndrome), based on the clinical course and imaging findings. DNA tests of her blood and cerebrospinal fluid revealed the presence of human herpesvirus 6. INTERVENTIONS: Pharmacotherapy and rehabilitation therapy. OUTCOME: Gross motor function has recovered considerably, but she had a mild developmental delay at 30 mo old. LESSONS: Hemiplegia due to AESD was extremely rare, and appropriate rehabilitation treatment resulted in recovery of physical function. However, as mild developmental delay was observed, the patient was referred to a specialized facility before entering school.

Mechanical stimulation is a risk factor for phlebitis associated with peripherally inserted central venous catheter in neonates.

BACKGROUND: Our peripherally inserted central venous catheter (PICC) management plan for neonates previously included routine inspection for swelling and induration of the insertion site of a PICC using palpation. However, we discontinued routine palpation from July 13, 2018, owing to a peculiarly high incidence of PICC-related phlebitis. The aim of this study was to prove that routine palpation was the cause of PICC-related phlebitis. METHODS: We retrospectively reviewed medical records of infants who were admitted to the neonatal intensive care unit and underwent PICC placement from January 2018 to January 2019. The infants were classified into palpating (before July 13, 2018) and non-palpating (after or on July 13, 2018) groups. We analyzed and compared the incidence of PICC-related phlebitis in the two groups. RESULTS: Phlebitis related to PICC was more frequently observed in the palpating group (10/29 infants, 34.5%) than in the non-palpating group (1/31, 3.2%) (P = 0.002). After discontinuation of routine palpating in PICC management, the frequency of non-scheduled removal of the PICC due to phlebitis decreased. The indwelling period was significantly longer in the non-palpating group than in the palpating group. CONCLUSIONS: Our results suggest that mechanical stimulation using palpation of the insertion site was the cause of PICC-related phlebitis, resulting in early non-scheduled removal.

Low threshold to Vestibular and Oral Sensory stimuli might affect quality of sleep among children with autism spectrum disorder.

AIMS: The current study aimed to validate the relationship between sensory characteristics and sleep dynamics among children with autism spectrum disorder (ASD) using an actigraph, which is an objective assessment device used for sleep monitoring. METHODS: A total of 40 children (age range, 3-6 years) participated in this study (n = 20, with ASD and n = 20, age-matched children with typical development [TD]). We examined sleep dynamics using actigraph for 7 consecutive days, and the relationship between sleep parameters and sensory characteristics was analyzed using the Japanese Version of Sensory Profile (SP-J). RESULTS: Significant differences were observed in terms of activities per minute during sleep (p = 0.02), sleep efficiency (SE) (p = 0.005), and wake after sleep onset (WASO) (p = 0.02) between the two groups. In the ASD group, significant positive correlations were observed between activities per minute during sleep and low thresholds for Vestibular Sensory stimuli (p = 0.046) and Oral Sensory stimuli (p = 0.006) using the SP-J. Based on a multiple regression analysis, the activities per minute during sleep were associated with low thresholds for Oral Sensory stimuli (ß = 0.51, t = 2.29, p = 0.03), but not with other factors, in the ASD group. CONCLUSIONS: The current study showed that atypical Vestibular and Oral Sensory modulation may be a risk indicator for high activities during sleep among preschool children with ASD. Thus, whether the interventions for these sensory characteristics are effective in improving sleep quality, daytime activities, behaviors, and cognitive functions in this group of children must be considered.

A case of early myoclonic encephalopathy with intractable seizures successfully treated with high-dose phenobarbital.

BACKGROUND: Early myoclonic encephalopathy (EME) is an epileptic syndrome that develops in neonates, commonly within 1 month of birth. The condition is characterized by irregular, partial, and asynchronous myoclonus. The seizures in EME are generally refractory to antiepileptic drugs and no effective treatment for EME has been established. We encountered a case of EME in which oral high-dose phenobarbital therapy effectively alleviated seizures. CASE REPORT: A male infant developed erratic myoclonus in the face and limbs, exhibited upward gaze and facial flushing 20-30 times a day since 1 week of age. Electroencephalogram (EEG) showed a burst-suppression pattern, and considering the clinical features, EME was diagnosed. Valproate and vitamin B6 treatments were initiated; however, they were not effective. At day 58 after birth, oral high-dose phenobarbital therapy was introduced which resulted in the suppression of seizures to one or two per week and disappearance of the burst-suppression pattern on EEG. CONCLUSION: Oral high-dose phenobarbital treatment may be suitable for controlling seizures in EME.

Risk Factors for the Development of Refeeding Syndrome-Like Hypophosphatemia in Very Low Birth Weight Infants.

BACKGROUND: Refeeding syndrome is characterized by metabolic disturbance including hypophosphatemia and hypokalemia upon reinstitution of nutrition in severely malnourished patients. OBJECTIVE: The present study sought to identify the risk factors for the development of refeeding syndrome-like metabolic disturbance in very low birth weight infants. METHODS: The correlations of severe hypophosphatemia with the serum levels of potassium and ionized calcium, daily calorie and phosphate intake, and umbilical cord blood flow on ultrasonography were analyzed in 49 very low birth weight infants. RESULTS: Fifteen infants (36%) presented with hypophosphatemia during the first postnatal week. Hypophosphatemia was significantly associated with birth weight z score (odds ratio, 1.60; 95% confidence interval, 1.04-2.47; p = 0.034) and umbilical artery resistance index (odds ratio, 7.72E-04; 95% confidence interval, 1.14E-06-0.523; p = 0.031). Multiple regression analysis revealed that umbilical artery resistance index was independently associated with hypophosphatemia. CONCLUSIONS: Umbilical artery resistance index may serve as a useful marker for future development of refeeding syndrome-like hypophosphatemia in very low birth weight infants. Close monitoring of serum phosphorus and potassium levels and early intervention are important for the management of very low birth weight infants with intrauterine growth restriction due to placental dysfunction.

Urinary podocalyxin as a possible novel marker of intrauterine nephrogenesis and extrauterine podocyte injury.

BACKGROUND: The number of nephrons at birth is determined during fetal development and is modulated thereafter by postnatal podocyte injury. Hyperfiltration, caused by a reduced number of nephrons, is a risk factor for chronic kidney disease. It is therefore important to monitor the formation of nephrons. METHODS: Urine samples were collected from infants within 1-2 days of birth, with follow-up sampling for preterm infants at 37-39 weeks of corrected age. Urinary levels of podocalyxin (PCX), ß2-microglobulin (ß2MG), N-acetyl-ß-D-glucosaminidase (NAG), total protein (TP), microalbumin (mAlb) and creatinine were measured and the relationship between these markers evaluated. RESULTS: Seventy-nine neonates were enrolled in this study. Urinary levels of PCX at birth were higher than normal adult reference values, with levels increasing up to a gestational age of 36 weeks (p = 0.0242). At 37-39 weeks corrected age, urinary levels of PCX decreased to adult levels. The levels of PCX in the urine at birth were not correlated to urinary levels of ß2MG, NAG, TP and mAlb. CONCLUSIONS: An increased urinary level of PCX may be a marker of both active nephron formation and podocyte injury sustained at birth. As such, changes in urinary levels of PCX are likely to reflect adaptation of renal function to the extra-uterine environment.

Treatment with Geranylgeranylacetone Induces Heat Shock Protein 70 and Attenuates Neonatal Hyperoxic Lung Injury in a Model of Bronchopulmonary Dysplasia.

PURPOSE: Bronchopulmonary dysplasia (BPD) is a respiratory complication characterized by abnormal alveolar development in premature infants. Geranylgeranylacetone (GGA) can induce heat shock protein (HSP) 70, which has cytoprotective effects against various stressors. Here, we investigated whether GGA protected neonatal lungs from hyperoxic stress in a murine BPD model, and measured the serum HSP70 levels in preterm humans treated with oxygen. METHODS: Newborn mice were exposed to >90% oxygen and administered GGA or vehicle alone orally on days 1, 2, and 3 of life. At 2 days of age, HSP70 expression in the lung was determined by western blotting. At 8 days of age, the lungs were processed for histological analysis. Radial alveolar count (RAC) and mean linear intercept (MLI) were measured as parameters of alveolarization. Apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method and cleaved caspase-3 immunohistochemistry. Serum HSP70 levels in preterm humans treated with oxygen were measured by enzyme-linked immunosorbent assay. RESULTS: GGA administration enhanced the HSP70 expression to two-fold compared with normoxia-exposed and vehicle-treated mice. Hyperoxia reduced HSP70 expression, whereas GGA abrogated the effects. Hyperoxia-exposed mice exhibited more apoptotic cells in lung parenchyma and a more simplified alveolar structure with less RAC and larger MLI than normoxia-exposed mice. GGA suppressed the increase in apoptotic cells and the structural changes of the lungs induced by hyperoxia. Serum HSP70 levels of preterm human infants gradually decreased with age. CONCLUSIONS: GGA may attenuate hyperoxic injury in neonatal lungs and thereby may prevent the development of BPD.

The Usefulness of T1-Weighted Magnetic Resonance Images for Diagnosis of Acute Leukemia Manifesting Musculoskeletal Symptoms prior to Appearance of Peripheral Blood Abnormalities.

The patients with acute leukemia occasionally present with musculoskeletal symptoms initially, including bone pain, joint pain, muscular pain, and functional impairment. Without abnormal findings of peripheral blood cell counts or smear, the correct diagnosis tends to be delayed. Magnetic resonance imaging is often performed to examine musculoskeletal abnormalities; it can simultaneously reveal the bone marrow composition with high anatomical resolution and excellent soft tissue contrast. We present 4 pediatric patients who were initially diagnosed with acute pyogenic osteomyelitis or arthritis, based on the elevated white blood cell counts and/or C-reactive protein in addition to the localized high signal intensity on T2-weighted magnetic resonance images. Finally, they were diagnosed with B-cell precursor acute lymphoblastic leukemia by bone marrow examination. The period between the onset of musculoskeletal symptoms and the diagnosis of leukemia ranged from 20 days to 6 months. In all cases, the T1-weighted magnetic resonance images taken prior to detection of peripheral blood abnormality revealed diffuse low signal intensity of the bone marrow in regions adjacent or contralateral to localized musculoskeletal symptoms. These findings should raise the suspicion of leukemia even without abnormalities in peripheral blood.

Postnatal Changes in Humerus Cortical Bone Thickness Reflect the Development of Metabolic Bone Disease in Preterm Infants.

Objective. To use cortical bone thickness (CBT) of the humerus to identify risk factors for the development of metabolic bone disease in preterm infants. Methods. Twenty-seven infants born at <32 weeks of gestational age, with a birth weight of <1,500 g, were enrolled. Humeral CBT was measured from chest radiographs at birth and at 27-28, 31-32, and 36-44 weeks of postmenstrual age (PMA). The risk factors for the development of osteomalacia were statistically analyzed. Results. The humeral CBT at 36-44 weeks of PMA was positively correlated with gestational age and birth weight and negatively correlated with the duration of mechanical ventilation. CBT increased with PMA, except in six very early preterm infants in whom it decreased. Based on logistic regression analysis, gestational age and duration of mechanical ventilation were identified as risk factors for cortical bone thinning. Conclusions. Humeral CBT may serve as a radiologic marker of metabolic bone disease at 36-44 weeks of PMA in preterm infants. Cortical bones of extremely preterm infants are fragile, even when age is corrected for term, and require extreme care to lower the risk of fractures.

Carboxyhemoglobin Formation in Preterm Infants Is Related to the Subsequent Development of Bronchopulmonary Dysplasia.

OBJECTIVE: To evaluate the usefulness of carboxyhemoglobin (CO-Hb) levels as a biomarker to predict the development and severity of bronchopulmonary dysplasia (BPD). METHODS: Twenty-five infants born at <33 wk of gestational age or with a birth weight of <1,500 g were enrolled. CO-Hb levels were measured between postnatal days 5 and 8, 12 and 15, 19 and 22, and 26 and 29. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products, and Nε-(hexanoyl) lysine were measured between postnatal days 5 and 8 and 26 and 29. Receiver operating characteristic (ROC) analysis was used to compare the biomarkers' predictive values. RESULTS: Compared with infants in the no-or-mild BPD group, infants with moderate-to-severe BPD exhibited higher CO-Hb levels during the early postnatal period and higher 8-OHdG levels between postnatal days 5 and 8. Using ROC analysis to predict the development of moderate-to-severe BPD, the area under the curve (AUC) for CO-Hb levels between postnatal days 5 and 8 was higher than AUCs for the urinary markers. CONCLUSIONS: CO-Hb levels during the early postnatal period may serve as a practical marker for evaluating oxidative stress and the severity of subsequently developing BPD.

[Assessment of brain perfusion by arterial spin-labeling MR imaging in qusai-moyamoya disease associated with Graves' disease].

We report a case of 12-year-old girl with Graves' disease who had presented with deterioration in physical and scholastic performances since 10 years of age. She had an episode of atonic seizure and difficulty in speech. Brain MRI revealed formation of moyamoya vessels and a lesion suggestive of ischemic changes in the left frontal lobe. Because of uncontrollable thyrotoxicosis with anti-thyroid drug, she received a subtotal thyroidectomy. Two months later, she received a shunt operation between left superficial temporal artery and middle cerebral artery. The postoperative arterial spin-labeling MR imaging demonstrated an improvement of brain perfusion in left frontal lobe compared with the preoperative one, and provided comparable results of angiography and acetazolamide-challenged 150-gas PET. Thus, arterial spin-labeling MR imaging seems useful for follow-up evaluation of brain perfusion in qusai-moyamoya disease.

Marked elevation of interleukin-6 in mild encephalopathy with a reversible splenial lesion (MERS) associated with acute focal bacterial nephritis caused by Enterococcus faecalis.

This report describes two cases of mild encephalitis/encephalopathy with reversible splenial lesion (MERS) associated with acute focal bacterial nephritis (AFBN). The patients, who presented with fever and delirious behavior, exhibited hyponatremia and markedly elevated interleukin (IL)-6 in cerebrospinal fluid (CSF) and serum. Enterococcus faecalis was detected in the urine culture. After ampicillin treatment, their consciousness improved without neurological sequelae. Moreover, a diffusion-weighted MRI abnormality, i.e., intensified signals in splenium of the corpus callosum, disappeared. MERS is a possible complication of AFBN. Elevated CSF IL-6 levels suggest that remote activation of intracerebral immune response through the immune-neuroendocrine pathway might play an important role in the pathophysiology of MERS.

[A male case of subcortical band heterotopia with somatic mosaicism of DCX mutation].

This report describes a male case of subcortical band heterotopia (SBH) with somatic mosaicism of doublecortin (DCX) mutation. His brain MRI revealed bilateral SBH with anterior dominant pachygyria. Although he had infantile spasms from 5-months old and showed mild developmental delay, he responded well to vitamin B6 and ACTH therapy. We conducted DCX mutation analysis using peripheral blood lymphocytes of the proband and his parents. Only the present case showed the mixture pattern of missense mutation (c. 167 G>C) and normal sequence of DCX gene indicating that the present case resulted from somatic mosaicism of de novo DCX mutation. Male patients with DCX mutations generally present with the classical type of lissencephaly, severe developmental delay, and intractable epilepsy. However, somatic mosaic mutation of DCX can lead to SBH in males.

Biotin and carnitine profiles in preterm infants in Japan.

BACKGROUND: Biotin plays an important role as a covalently bound coenzyme for carboxylases. Carnitine is essential in ß-oxidation to transport long-chain fatty acids across the inner mitochondrial membrane. The present study was conducted to assess the risk of biotin and carnitine deficiencies in preterm infants who received enteral feeding with maternal milk and/or standard infant formula made in Japan. METHODS: Forty-six infants were enrolled in the study. Urine and serum samples and dried blood spots were collected at 1 week and 1 month of age. Additionally, samples were collected at 40 and 44 weeks post-menstrual age (PMA) in preterm infants. Free carnitine and C5-OH acylcarnitine, which consist of 3-hydroxyisovalerylcarnitine as a major isomer, were measured in serum samples and dried blood spots using tandem mass spectrometry. Urine 3-hydroxyisovaleric acid (3-HIVA) was measured using gas chromatography/mass spectrometry. RESULTS: The free carnitine levels in preterm infants were significantly lower than those in term infants, but increased with PMA in serum samples and dried blood spots. C5-OH acylcarnitine and urinary 3-HIVA levels, which were very low in term infants, were increased with PMA in preterm infants. CONCLUSION: The present results may indicate chronic biotin deficiency in preterm infants fed maternal milk and/or standard infant formula. Analyses of carnitine profiles of dried blood spots and urine 3-HIVA are relatively non-invasive and useful for the early detection of biotin deficiency in preterm infants.