Prolonged N200 is the early neurophysiologic change in the patient with minimal hepatic encephalopathy.

BACKGROUND: In neurophysiological studies, P300, is well known for reflecting early cognitive impairment in minimal hepatic encephalopathy (MHE). Although P300 is investigated extensively, other early event-related potential (ERP) parameters have not been studied in MHE. METHODS: The subjects were 21 adult cirrhotic patients without clinical encephalopathy and 29 normal controls. For neuropsychological testing, number connection tests, A and B (NCT-A, NCT-B), the line tracing test, the serial dotting test (SDT), and the digit symbol test (DST) were performed. For ERP testing, auditory oddball paradigms were used. The N100, P200, N200, and P300 parameters were measured. RESULTS: Cirrhosis had longer neuropsychological performance scores on NCT-A, SDT, and DST than the control group. In neurophysiological test, cirrhotic patients showed longer latencies for N100, P200, N200, and P300 than the control group. Although P300 alteration was not seen in patients without MHE compared to the control group (325.4±43.3 vs. 345.21±35.1, p=0.25), N200 latency was significantly prolonged in cirrhotic patients without MHE compared to the healthy group (242.1±30.3 vs. 259.58±33.3, p=0.006). N200 also showed good correlation with psychometric hepatic encephalopathy score and critical flicker frequency. CONCLUSIONS: N200 is a useful tool for assessing early changes of cognitive dysfunction in cirrhosis. It suggests that slower auditory cortical processing is the first sign of cerebral deterioration in patients with hepatic encephalopathy.

Practical application of kangaroo mother care in preterm infants: clinical characteristics and safety of kangaroo mother care.

AIM: To determine the clinical characteristics and safety of kangaroo mother care (KMC) according to the gestational age (GA) or postmenstrual age (PMA). METHODS: We conducted a prospective clinical study in 31 infants between 25 and 32 weeks' GA. The subjects were categorized into two groups (25-28 weeks' and 29-32 weeks' GA groups) to compare the clinical characteristics associated with KMC. Heart rate, respiratory rate, oxygen saturation, blood pressure and body temperature (BT) were longitudinally assessed for 60 min with respect to the PMA group (29-32 weeks' and 33-36 weeks' PMA groups). RESULTS: The authors analyzed 70 sessions with 31 infants (25-32 weeks' GA, birth weight 760-1740 g, 29-36 weeks' PMA). All infants had statistically significant higher temperatures during KMC than before KMC within clinically acceptable limits (P<0.001). We found a significantly lower variation of BT in the 25-28 weeks' GA group compared with the 29-32 weeks' GA group at 33-36 weeks' PMA, suggesting accelerated skin maturation in more premature infants (P<0.001). CONCLUSION: Our intermittent KMC was a safe and feasible method for preterm infants. Notably, at the same PMA, preterm infants in the lower at-birth GA group showed an advanced maturation of thermoregulation compared with those in the higher GA group.

Human parathyroid hormone increases the mRNA expression of the IGF system and hematopoietic growth factors in osteoblasts, but does not influence expression in mesenchymal stem cells.

Osteoblasts, which are derived from pluripotent mesenchymal stem cells (MSCs), play an important role in hematopoiesis. Human parathyroid hormone (hPTH) induces osteoblasts to produce many factors that are essential to hematopoietic stem cells. However, little is known about the impact of hPTH on MSCs to enhance hematopoiesis. We determined the optimal dose of hPTH that was necessary in vitro for increased osteoblast function. In addition, we compared MSC and osteoblast function to explore the role of hPTH in hematopoiesis. The mRNA expression levels of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 6, stromal cell-derived factor 1, insulin-like growth factor 1 (IGF-1), IGF-2, insulin-like growth factor-binding protein 1 (IGFBP-1), IGFBP-2, and IGFBP-3 were comparable in osteoblasts and human cord blood-derived MSCs. However, G-CSF, GM-CSF, IGF-2, IGFBP-1, IGFBP-2, and IGFBP-3 expression levels in osteoblasts were markedly increased after treatment with 50 or 100 nM of hPTH. In conclusion, hPTH does not affect the ability of MSCs to differentiate into osteoblasts. In addition, hPTH may enhance hematopoiesis by activating the IGF system (IGF-2, IGFBP-1, IGFBP-2, and IGFBP-3) and hematopoietic growth factors (G-CSF and GM-CSF) in osteoblasts, but not in MSCs.

Protective effect of hypoxic preconditioning on hypoxic-ischemic injured newborn rats.

Brief episodes of cerebral hypoxia-ischemia cause transient ischemic tolerance to subsequent ischemic events that are otherwise lethal. This study was conducted to evaluate the protective effect of hypoxic preconditioning on hypoxic-ischemic injury in the neonatal rat and the persistence of a protective window after hypoxic preconditioning. The rats were preconditioned with hypoxia (8% oxygen, 92% nitrogen) for three hours, subjected to ischemia using ligation of the right common carotid artery, and then exposed to another three hours of hypoxia. Using proton magnetic resonance spectroscopy, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining, and morphologic scores, this study shows that hypoxic preconditioning 6-hr to 1-day before hypoxic-ischemic injury increases survival rates and has neuroprotective effects against subsequent hypoxic-ischemic injury. The mechanism of the protective effects of hypoxic preconditioning in the newborn rat brain may involve downregulation of apoptotic cell death.

Hypohidrosis-related symptoms in pediatric epileptic patients with topiramate.

BACKGROUND: Topiramate is one of the most commonly prescribed newer antiepileptic drugs. However, we have encountered quite a few cases of pediatric epileptic patients on topiramate complaining about the symptoms related to hypohidrosis. The aim of this study was to determine the incidence and define the clinical characteristics of hypohidrosis-related symptoms with topiramate in pediatric patients. METHODS: Data was collected prospectively on 264 patients diagnosed as having epilepsy and treated with topiramate at the Department of Pediatrics, Chonbuk National University Hospital between July 2004 and July 2006. The data were collected by direct interview after at least 3 months had elapsed from the initiation of the medication. RESULTS: The study group was composed of 70 boys and 81 girls, with a mean age of 33.1 +/- 43.2 months. The mean duration of topiramate treatment was 13.4 +/- 15.0 months; 52 patients (34.4%) were treated with topiramate only and 99 patients (65.6%) were on polytherapy including topiramate; 59 out of 151 patients (39.1%) experienced hypohidrosis-related symptoms: such as facial flushing, lethargy, itching sensation, irritability with hyperthermia, heat sensation or heat intolerance. However, there were no patients complaining of hypohidrosis-related symptoms among those who were taking antiepileptic drugs other than topiramate. CONCLUSIONS: Our results suggest that topiramate induces hypohidrosis-related symptoms more often than we expected, especially in pediatric patients. We recommend that pediatric epileptic patients taking topiramate should be warned to avoid hot and humid environments, especially during the hot summer season.

Respiratory syncytial virus-associated seizures in Korean children, 2011-2016.

PURPOSE: Respiratory syncytial virus (RSV) infection can cause various neurological complications. This study aimed to investigate the RSV-associated neurologic manifestations that present with seizures. METHODS: We retrospectively reviewed the medical records of patients aged less than 15 years with laboratory-confirmed RSV infections and seizures between January 2011 and December 2016 in a regional hospital in South Korea. RESULTS: During this period, 1,193 patients with laboratory-confirmed RSV infection were identified. Of these, 35 (35 of 1,193, 2.93%; boys, 19; girls, 16; mean age: 20.8±16.6 months) presented with seizures. Febrile seizure was the most common diagnosis (27 of 35, 77.1%); simple febrile seizure in 13 patients (13 of 27, 48.1%) and complex febrile seizure in 14 (14 of 27, 51.9%). Afebrile seizures without meningitis or encephalopathy were observed in 5 patients (5 of 35, 14.3%), seizures with meningitis in 2 (2 of 35, 5.7%), and seizure with encephalopathy in 1 (1 of 35, 2.9%) patient. Lower respiratory symptoms were not observed in 8 patients. In a patient with encephalopathy, brain diffusion-weighted magnetic resonance imaging revealed transient changes in white matter, suggesting cytotoxic edema as the mechanism underlying encephalopathy. Most patients recovered with general management, and progression to epilepsy was noted in only 1 patient. CONCLUSION: Although febrile seizure is the most common type of seizure associated with RSV infection, the proportion of patients with complex febrile seizure was higher than that of general febrile seizure. Transient cytotoxic edema may be a pathogenic mechanism in RSV-related encephalopathy with seizures.

The Akt/mTOR/p70S6K Pathway Is Involved in the Neuroprotective Effect of Erythropoietin on Hypoxic/Ischemic Brain Injury in a Neonatal Rat Model.

BACKGROUND: The mTOR (mammalian target of rapamycin) signaling pathway is a master regulator of cell growth and proliferation in the nervous system. However, the effects of erythropoietin (EPO) treatment on the mTOR signaling pathway have not been elucidated in neonates with hypoxic/ischemic (H/I) brain injury. OBJECTIVES: We investigated the mechanism underlying the neuroprotective effect of EPO by analyzing the mTOR signaling pathway after H/I injury in a neonatal rat model. METHODS: Seven-day-old rats were subjected to left carotid artery ligation and hypoxic exposure (8%) for 90 min (H/I). EPO at a dose of either 3,000 U/kg or a vehicle (V) was administered by intraperitoneal injection 0, 24 and 48 h after H/I. At 72 h after H/I (postnatal day 10), 2,3,5-triphenyltetrazolium chloride staining, myelin basic protein (MBP) immunofluorescence staining and Western blot analysis of the Akt/mTOR/p70S6K pathway were performed. Neuromotor behavioral tests included Rotarod challenge and cylinder rearing test 1 performed 3 and 6 weeks after H/I. RESULTS: EPO treatment resulted in significant offsetting of MBP depletion ipsilateral (p = 0.001) and contralateral (p = 0.003) to ligation. Western blot analysis showed that the relative immunoreactivity of phosphorylated (p)-Akt, p-mTOR and p-p70S6K ipsilateral to ligation was significantly decreased in the H/I+V group compared with the sham-operated groups. However, EPO treatment significantly upregulated Akt/mTOR/p70S6K signals ipsilateral to ligation compared to the H/I+V group. The behavior tests showed that EPO attenuates long-term impairment in Rotarod challenge and cylinder test performance from 3-6 weeks. CONCLUSION: This study demonstrates an underlying mechanism of the mTOR signaling pathway after EPO treatment, which is a potential target for treating H/I-induced brain injury.

A new mosaic der(18)t(1;18)(q32.1;q21.3) with developmental delay and facial dysmorphism.

We report the case of a 22-month-old boy with a new mosaic partial unbalanced translocation of 1q and 18q. The patient was referred to our Pediatric Department for developmental delay. He showed mild facial dysmorphism, physical growth retardation, a hearing disability, and had a history of patent ductus arteriosus. White matter abnormality on brain magnetic resonance images was also noted. His initial routine chromosomal analysis revealed a normal 46,XY karyotype. In a microarray-based comparative genomic hybridization (aCGH) analysis, subtle copy number changes in 1q32.1-q44 (copy gain) and 18q21.33-18q23 (copy loss) suggested an unbalanced translocation of t(1;18). Repeated chromosomal analysis revealed a low-level mosaic translocation karyotype of 46,XY,der(18)t(1;18)(q32.1;q21.3)[12]/46,XY[152]. Because his parents had normal karyotypes, his translocation was considered to be de novo. The abnormalities observed in aCGH were confirmed by metaphase fluorescent in situ hybridization. We report this patient as a new karyotype presenting developmental delay, facial dysmorphism, cerebral dysmyelination, and other abnormalities.

Neurological and muscular manifestations associated with influenza B infection in children.

BACKGROUND: Influenza viruses have been associated with various neurological and muscular symptoms. The aim of this study was to evaluate the pediatric neurological and muscular manifestations of influenza B during a 5-month epidemic at a single center. METHODS: We retrospectively reviewed the medical records of 355 pediatric patients with laboratory-confirmed influenza B infection. RESULTS: Neurological and muscular symptoms were exhibited by 28 patients (7.9%). The mean age was 48.7 ± 25.2 months. The mean time between respiratory symptoms and neurological symptoms was 2.2 ± 1.5 days. The most common symptom was seizure (19/28, 67.9%), followed by myositis (5/28, 17.9%), increased intracerebral pressure (1/28, 3.6%), delirium (1/28, 3.6%), and severe headache (1/28, 3.6%). There was one severe case of meningitis with myocarditis (1/28, 3.6%). All seizures were febrile: 15 simple febrile seizures (78.9%), three complex febrile seizures (15.8%), and one febrile status epilepticus (5.3%). The mean age of nine patients with their first seizures was 37.9 ± 22.2 months, which was older than the typical age of onset for febrile seizure. All the patients, except one, were treated with oseltamivir. There were no deaths or chronic debilitating sequelae. CONCLUSIONS: The neurological and muscular complications of influenza B infection in children are relatively mild, and febrile seizure is the most common. However, clinicians should be alert to the possibility of rare severe complications during influenza B outbreaks.

Acoustic effects of lamotrigine in pediatric patients with epilepsy.

The aim of this study was to investigate the acoustic effects of lamotrigine in pediatric epileptic patients. Newly diagnosed 52 pediatric epileptic patients were assessed standard speech test through a Computerized Speech Lab applied before the beginning of therapy with lamotrigine and 2months after dosage had been stabilized. The voice onset times for /t/, /k(h)/, /p'/ and /t'/ after the therapy and those for /p/, /k/, /p(h)/, /t(h)/ and /k'/ was not affected. Total durations for all stop consonants did not change significantly except that lenis /p/ and /k/ increased significantly (P<0.05). No noteworthy alteration was observed for mean pitch and speaking rate of counting 1-10. Vowel formants and precise articulation rate remained the same. In conclusion, no significant effects of lamotrigine on speech were found in this study. Lamotrigine is safe for acoustic function in pediatric patients.

Clinical features of encephalopathy in children with cancer requiring cranial magnetic resonance imaging.

We analyzed acute neurotoxic problems attributable to chemotherapy or immunosuppression in the context of childhood neoplastic diseases, based on clinical and neuroradiologic findings. This retrospective single-center study reviewed the acute neurologic complications of 62 children receiving conventional chemotherapy or hematopoietic stem cell transplantation from July 2005-July 2008. We excluded patients with central nervous system metastasis and various neurotoxic manifestations not usually requiring cranial magnetic resonance imaging. Of 62 patients, 12 (19.3%) developed acute neurologic complications. The most common complications included posterior reversible encephalopathy syndrome in six of 12 (50%) patients, and Wernicke's encephalopathy in three of 12 (25%) patients. Other complications included chemical arachnoiditis, grey matter injury induced by postchemotherapeutic angiopathy, and leukoencephalopathy. Posterior reversible encephalopathy syndrome was accompanied by hypertensive episodes in most patients (5/6), and Wernicke's encephalopathy was evident with altered mental status in malnourished children. These data indicate that posterior reversible encephalopathy syndrome and Wernicke's encephalopathy are the predominant complications in children undergoing chemotherapy or hematopoietic stem cell transplantation. Early radiologic and clinical evaluation and prompt treatment for these complications are necessary to prevent their progression to irreversible brain damage.