Arterial ischemic stroke in children with congenital heart diseases.

BACKGROUND: We describe the prevalence, thromboembolic risk factors, and neurologic outcomes in children with congenital heart disease (CHD) and arterial ischemic stroke (AIS). METHODS: We retrospectively analyzed the clinical data of children with CHD and AIS from 2000 to 2016. Demographics, procedural and postprocedural data, neuroimaging findings, details of antithrombotic treatment, and neurological status at last follow up were evaluated. RESULTS: Patients with cyanotic CHD accounted for 24 of 30 cases with AIS. The majority of AIS (70%) was procedure related, and the mean time from procedure to diagnosis of stroke was 9.7 (range, 1-30) days. At the time of AIS, 14 (46.7%) patients revealed coexistence of additional thromboembolic causes of AIS. Three patients (10.0%) experienced recurrent AIS and six patients (20.0%) were diagnosed with post-stroke epilepsy. The unfavorable outcomes were found in 13 patients (43.3%), including four deaths. The unfavorable outcome was significantly associated with the main branch involvement of middle cerebral artery (OR = 10.296, 95% CI = 1.335-79.439) and hemorrhagic transformation (OR = 16.264, 95% CI = 1.359-194.690). CONCLUSIONS: Additional thromboembolic risk factors such as systemic or cardiac thrombus, arrhythmia, and surgical procedures for cyanotic CHD were found in patients with CHD and AIS. The main branch involvement of middle cerebral artery and hemorrhagic transformation were significant predictors of unfavorable outcomes. Further studies are required to identify the target for stroke prevention and develop better prophylactic strategies to minimize AIS in patients with CHD.

Fast oscillation dynamics during hypsarrhythmia as a localization biomarker.

Hypsarrhythmia in West syndrome, although hard to define, is characterized by chaotic and disorganized electrical activity of the brain and is often regarded as a generalized EEG pattern without any localization value. Using event-related spectral perturbation (ERSP), we tried to determine the brain dynamics during hypsarrhythmia. Routine 1-h scalp EEGs were retrieved from 31 patients with infantile spasms and 20 age-matched controls. Using the EEGLAB toolbox of MATLAB 2015b, the ERSPs of fast oscillations (FOs; 20-100 Hz) of selected channels were analyzed and compared among groups according to their MRI lesions. FO-ERSP cutoff values for predicting the pathologic foci were estimated. The mean FO-ERSPs across all analyzed electrodes of patients with spasms were significantly higher than those of controls. When the patients were categorized into nonlesional, focal/multifocal, or diffuse lesional groups, the FO-ERSP of patients in the focal/multifocal lesional group was significantly lower than that of those in the nonfocal or diffuse lesional groups. In the focal/multifocal lesional group, seven patients (7/9, 77.8%) showed that the locations of channels with high FO-ERSPs were matched to the pathologic MRI lesions. Thus, the localization of high FO-ERSPs is closely associated with the location of pathologic brain lesions. Further research is required to prove the value of the FO-ERSP as an important quantitative localizing biomarker of West syndrome. NEW & NOTEWORTHY The locations of high fast oscillation-event-related spectral perturbations (FO-ERSPs) are closely associated with brain pathologic lesions, and high FO-ERSPs can be used as a localization biomarker of pathologic brain lesions in patients with hypsarrhythmia. With further validation, FO-ERSP might be useful as a biomarker for the localization of hidden pathologies in conditions with generalized epileptiform activities such as West syndrome.

Continuous myocloni and tonic spasms in a 2-month-old infant with enterovirus 71 brain stem encephalitis.

Brain stem encephalitis is a cardinal presentation of central nervous system involvement in enterovirus 71 infection, and manifests as myoclonus, ataxia, tremor, and autonomic dysfunction. A 2-month-old infant with enterovirus 71 brain stem encephalitis demonstrated continuous myocloni and tonic spasms. On admission, the patient's myoclonus, which mainly involved the shoulders and the arms, was considerably worse during wakefulness and occurred once or twice a minute. Several hours after admission, the myoclonic jerks steadily worsened, appeared ceaselessly every 1 to 2 seconds, and were intermixed with tonic spasms of all four extremities accompanied by crying. Video electroencephalography revealed a normal background without epileptiform discharges and no ictal electroencephalographic changes during the myoclonic jerks and tonic spasms. Complete remission was achieved without complications after completion of a 3-day immunoglobulin therapy. This case suggests that the brain stem may be a major origin site for not only myoclonus but also tonic spasm.

Antimicrobial susceptibility testing of two Lawsonia intracellularis isolates associated with proliferative hemorrhagic enteropathy and porcine intestinal adenomatosis in South Korea.

This study represents the first published data on antimicrobial susceptibility of Asian isolates of Lawsonia intracellularis. We assessed MICs of 16 antimicrobials for two isolates of L. intracellularis recovered from diseased pigs in South Korea, one from a finisher pig with acute proliferative hemorrhagic enteropathy in 2002 and the other from a grower pig with porcine intestinal adenomatosis in 2010. Tylosin and tilmicosin were found to be the most active against L. intracellularis both intracellularly (MICs, 0.25 to 0.5 µg/ml and 0.125 µg/ml, respectively) and extracellularly (MICs, 0.25 to 0.5 µg/ml and 1 µg/ml, respectively).

A long-term subacute sclerosing panencephalitis survivor treated with intraventricular interferon-alpha for 13 years.

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, and fatal central nervous system disorder resulting from persistent measles virus infection. Long-term data are scarce, with a maximum follow-up period of 10 years. Interferon-alpha (IFN-α) is a protein that exerts its antiviral activity via enhancement of cellular immune response and is reported to be an effective drug for the treatment of SSPE. However, there is currently no consensus regarding the optimal duration of IFN-α therapy. Here, we present a case report of a patient with SSPE treated with long-term intraventricular IFN-α therapy, which facilitated clinical improvement and neurological stabilization without causing serious adverse effects. To the best of our knowledge, this is one of the longest follow-up studies investigating a patient with SSPE receiving intraventricular INF-α treatment. Further studies are necessary to validate the benefits and safety of long-term intraventricular IFN-α treatment in patients with SSPE.

Brain Magnetic Resonance Imaging Findings of Congenital Cytomegalovirus Infection as a Prognostic Factor for Neurological Outcome.

BACKGROUND: The aim of this study is to predict the neurological outcomes of patients with congenital cytomegalovirus infection by analysis of magnetic resonance images of the brain. METHODS: From June 2007 to June 2016, 31 patients were diagnosed with symptomatic congenital cytomegalovirus infection at Asan Medical Center. The medical records and magnetic resonance imaging (MRI) findings of these patients were reviewed, and the relationships between MRI findings and neurological outcomes were analyzed. RESULTS: Of the 31 patients, 17 were male and 12 were born prematurely (gestation age less than 37 weeks). Twenty-one patients presented with delayed development, 11 with microcephaly, and 10 with sensorineural hearing loss. Eleven patients developed epilepsy. The most common abnormal findings on brain MRI were ventriculomegaly (N = 21, 67.7%) and polymicrogyria (N = 14, 45.2%). Delayed development significantly correlated with the presence of polymicrogyria (P = 0.001). Epilepsy was significantly associated with polymicrogyria (P = 0.012), ventriculomegaly (P = 0.045), calcification (P = 0.006), and white matter abnormalities (P = 0.018). Sensorineural hearing loss was not associated with any abnormal findings on brain MRI. Based on these data, a new brain magnetic resonance cytomegalovirus scoring scale was built and this scoring scale can predict the development of epilepsy with odds ratio 3.62 (confidence interval 1.52 to 8.67, P = 0.004). CONCLUSIONS: In patients with congenital cytomegalovirus infections, brain MRI abnormalities could predict poor developmental outcomes and epilepsy, but not sensorineural hearing loss. Stratified magnetic resonance findings can be suggested as the predictors of neurological outcomes in individuals with congenital cytomegalovirus infections.

Pharmacokinetic and Pharmacodynamic Evaluation of Intravenous Levetiracetam in Children With Epilepsy.

This study aimed to evaluate the safety and tolerability of intravenous (IV) levetiracetam (LEV) as a monotherapy in children aged 1 month-16 years and to explore the pharmacokinetics (PK) of IV LEV and the time to seizure after IV then oral administration of LEV in pediatric children with epilepsy. Children diagnosed with acute unprovoked seizures requiring in-hospital IV LEV administration were included. After administration, the clinical seizure outcomes, side effects, and the Korean-Child Behavior Checklist were monitored and the PK and repeated time to seizure were analyzed via modeling using NONMEM software. Overall, 37 children with epilepsy were enrolled and underwent a PK analysis (median age, 4.6 years; median weight, 18.0 kg). Nine children (24.3%) had seizure recurrence during the follow-up period (median, 3.8 months) and 5 children (13.5%) experienced LEV-associated adverse events such as irritability (n = 2; 5.4%) and somnolence (n = 3; 8.1%). The plasma LEV concentrations after IV LEV were best described by a one-compartment linear PK model. Only body weight was associated with both the clearance and volume of distribution of LEV. The Weibull distribution model described the time to seizure recurrence well; no statistically significant predictor for the time to seizure was identified. Therefore, IV LEV was a well-tolerated and effective alternative in children with acute unprovoked seizures, and models for the PK and time to repeated seizure recurrence after LEV were successfully developed. In particular, the current use of a weight-based IV LEV dosing regimen in pediatric children is practical.

Neurodevelopmental outcomes in children with prenatally diagnosed corpus callosal abnormalities.

OBJECTIVE: Although corpus callosal abnormalities are among the most common brain malformations detected prenatally, few previous studies have described the neurodevelopmental outcomes of children with this condition. The aim of our study was to evaluate the neurodevelopmental outcomes and associated clinical features of children with corpus callosal abnormalities diagnosed by prenatal ultrasonography. METHODS: Between July 2011 and July 2016, forty-nine children with corpus callosal abnormalities were born in Asan Medical Center Children's Hospital. Neurodevelopmental assessments were conducted in 40 patients at a median age of 24.8 months using the Bayley Scales of Infant Development II or the Korean Infant and Child Development Test. Patients were categorized according to their postnatal magnetic resonance imaging (MRI) findings and accompanying anomalies. Baseline characteristics and developmental outcomes of each group were compared. RESULTS: Isolated agenesis or hypoplasia of the corpus callosum was found in 16 (32.7%) patients, other associated central nervous system (CNS) abnormalities were found in 28 (57.1%) patients, and non-CNS abnormalities were found in 11 (22.4%) patients. Among the 40 patients who underwent developmental assessment, 18 (45.0%) showed normal development and 10 (25.0%) showed moderate-to-severe global developmental delay. Seven of the twelve (58.3%) patients with isolated corpus callosal abnormalities showed normal development. The combination of corpus callosal abnormalities with non-CNS anomalies was significantly associated with developmental delay (odds ratio 2.5, 95% confidence interval 1.6-3.9, p = 0.001). Conversely, children with isolated corpus callosal abnormalities showed relatively favorable neurodevelopmental outcomes. CONCLUSION: Appropriate evaluation and comprehensive therapeutic approaches are strongly recommended for neonates who present with corpus callosal abnormalities combined with additional anomalies.

Short-Term Outcome of Intravenous Methylprednisolone Pulse Therapy in Patients With Infantile Spasms.

BACKGROUND: Many studies advocate hormonal treatments including high-dose oral prednisolone as an effective treatment for epileptic spasms. However, little is known about the effects of intravenous methylprednisolone pulse therapy on infantile spasms. We investigated the short-term response to intravenous methylprednisolone pulse therapy for the treatment of infantile spasms. METHODS: Patients with newly diagnosed infantile spasms and hypsarrhythmia on electroencephalography (EEG) at two tertiary centers in Korea were included. Patients received intravenous infusions of 30 mg/kg/day methylprednisolone for three days with tapering doses of oral prednisolone for two to four weeks for the treatment of infantile spasms. Response to methylprednisolone pulse therapy was evaluated by seizure frequency and follow-up EEG within three weeks. RESULTS: Fourteen patients were sudied. The mean age at the onset of spasms was 7.0 months (range, 2.0 to 11.0 months). Etiological factors included structural abnormalities (N = 11), chromosomal anomaly (N = 1), and unknown (N = 2). Nine of 14 participants (64.3%) demonstrated complete freedom from spasm and resolution of hypsarrhythmia on EEG within 3 weeks; however, only five of nine responders (55.5%) remained free of spasms after the discontinuation of oral steroids. Adverse effects, including irritability or infection, were observed in four patients but were tolerable in all. CONCLUSIONS: Short-term methylprednisolone pulse therapy for the treatment of infantile spasms or hypsarrhythmia demonstrated rapid improvement in EEG and cessation of spasms without serious adverse effects. Further studies are needed to determine the long-term effects of spasm control.