Dedicated neuroimaging analysis in children with primary headaches: prevalence of lesions and a comparison between patients with and without migraines.

BACKGROUND: This study evaluated the prevalence and types of intracranial lesions through dedicated imaging analysis of primary headaches in children and compared them between patients with and without migraine. METHODS: This study included 190 children diagnosed with primary headache who underwent neuroimaging, including brain computed tomography (CT), CT angiography (CTA), and brain magnetic resonance imaging (MRI). All patients with primary headaches was divided into two groups, namely, the migraine and non-migraine groups, on the basis of data from electronic medical records. Clinical characteristics and imaging findings were evaluated and compared between the two groups. RESULTS: Patients with migraine were old and had a longer period from symptom onset to diagnosis. CT was normal in 71 of 95 patients, whereas 7 of 29 patients who underwent CTA had vascular lesions; the migraine group (n = 6/20, [30%]) had higher incidence of vascular lesions than the non-migraine group (n = 1/9, [11.1%]); however, there was no statistically significant difference (p = 0.382). Furthermore, 57.5% (61/106) of children showed normal brain MRI. The most common brain MRI finding was dilated perivascular space (n = 18, [16.8%]). Most perivascular spaces were located in the basal ganglia (n = 72, [75.8%]) and were in linear patterns (n = 58, [63.0%]). There was no statistically significant difference between the two groups. CONCLUSION: A low prevalence of significant abnormalities was found in children with primary headaches. Dilated perivascular space was the most common finding in both groups on MRI. CTA showed more vascular lesions in the migraine group than in the non-migraine group. Therefore, further evaluations are needed to reveal the relationship between vascular lesions or dilated perivascular space and pediatric primary headaches.

Comparative analysis of background EEG activity based on MRI findings in neonatal hypoxic-ischemic encephalopathy: a standardized, low-resolution, brain electromagnetic tomography (sLORETA) study.

BACKGROUND: It is important to assess the degree of brain injury and predict long-term outcomes in neonates diagnosed with hypoxic-ischemic encephalopathy (HIE). However, routine studies, including magnetic resonance imaging (MRI) and conventional encephalography (EEG) or amplitude-integrated EEG (aEEG), have their own limitations in terms of availability and accuracy of evaluation. Recently, quantitative EEG (qEEG) has been shown to improve the predictive reliability of neonatal HIE and has been further refined with brain mapping techniques. METHODS: We investigated background EEG activities in 29 neonates with HIE who experienced therapeutic hypothermia, via qEEG using a distributed source model. MRI images were evaluated and classified into two groups (normal-to-mild injury vs moderate-to-severe injury), based on a scoring system. Non-parametric statistical analysis using standardized low-resolution brain electromagnetic tomography was performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between the two groups. RESULTS: Electrical neuronal activities were significantly lower in the moderate-to-severe injury group compared with the normal-to-mild injury group. Background EEG activities in moderate-to-severe HIE were most significantly reduced in the temporal and parietal lobes. Quantitative EEG also revealed a decrease in background activity at all frequency bands, with a maximum in decrease in the delta component. The maximum difference in current density was found in the inferior parietal lobule of the right parietal lobe for the delta frequency band. CONCLUSIONS: Our study demonstrated quantitative and topographical changes in EEG in moderate-to-severe neonatal HIE. They also suggest possible implementation and evaluation of conventional EEG and aEEG in neonatal HIE. The findings have implications as biomarkers in the assessment of neonatal HIE.

Comparative analysis of background EEG activity in juvenile myoclonic epilepsy during valproic acid treatment: a standardized, low-resolution, brain electromagnetic tomography (sLORETA) study.

BACKGROUND: By definition, the background EEG is normal in juvenile myoclonic epilepsy (JME) patients and not accompanied by other developmental and cognitive problems. However, some recent studies using quantitative EEG (qEEG) reported abnormal changes in the background activity. QEEG investigation in patients undergoing anticonvulsant treatment might be a useful approach to explore the electrophysiology and anticonvulsant effects in JME. METHODS: We investigated background EEG activity changes in patients undergoing valproic acid (VPA) treatment using qEEG analysis in a distributed source model. In 17 children with JME, non-parametric statistical analysis using standardized low-resolution brain electromagnetic tomography was performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between untreated and treated conditions. RESULTS: VPA reduced background EEG activity in the low-frequency (delta-theta) bands across the frontal, parieto-occipital, and limbic lobes (threshold log-F-ratio = ±1.414, p < 0.05; threshold log-F-ratio= ±1.465, p < 0.01). In the delta band, comparative analysis revealed significant current density differences in the occipital, parietal, and limbic lobes. In the theta band, the analysis revealed significant differences in the frontal, occipital, and limbic lobes. The maximal difference was found in the delta band in the cuneus of the left occipital lobe (log-F-ratio = -1.840) and the theta band in the medial frontal gyrus of the left frontal lobe (log-F-ratio = -1.610). CONCLUSIONS: This study demonstrated the anticonvulsant effects on the neural networks involved in JME. In addition, these findings suggested the focal features and the possibility of functional deficits in patients with JME.

Mimicking Hypoxic-Ischemic Encephalopathy in a Newborn with 21q Deletion Originating from Ring Chromosome 21.

Partial deletion of the long arm (q) in chromosome 21 is an extremely rare condition with various phenotypes, including microcephaly, neurodevelopmental delay, dysmorphic features, and epileptic seizures. Neonatal hypoxic-ischemic encephalopathy (HIE) is an encephalopathy associated with a hypoxic-ischemic event in the brain where seizures usually occur in the earliest days of life. Neonatal encephalopathy is a distinct entity resulting from metabolic disorders, congenital infections or genetic abnormalities that could often mimic HIE features, leading to a misdiagnosis of HIE. Here, we present a case of a newborn who was initially misdiagnosed with HIE due to HIE-like features, and eventually was diagnosed to have a de novo ring chromosome 21 with 21q microdeletion. Clinical findings, including severe hypotonia with respiratory/feeding difficulties and intractable seizures, and radiologic findings of ischemic encephalopathy were discovered. Subsequent atypical findings of the clinical presentation ultimately led to her undergoing genetic testing confirming that she had a neonatal encephalopathy with a genetic abnormality. Our case highlights the importance of identifying non-HI neonatal encephalopathy by careful and structured evaluation for current history with a clinical course and a multidisciplinary approach including genetic testing, to provide an accurate diagnosis, treat curable inherited disorders, and develop future genetic counseling.

Survival Prediction Model for Patients with Hepatocellular Carcinoma and Extrahepatic Metastasis Based on XGBoost Algorithm.

Purpose: Accurate estimation of survival is of utmost importance in patients with hepatocellular carcinoma (HCC) and extrahepatic metastasis. This study aimed to develop a survival prediction model using real-world data. Patients and Methods: A total of 993 patients with treatment-naïve HCC and extrahepatic metastasis were included from 13 Korean hospitals between 2013 and 2018. Patients were randomly divided into a training set (70.0%) and a test set (30.0%). The eXtreme Gradient Boosting (XGBoost) algorithm was applied to predict survival at 3, 6, and 12 months. Results: The mean age of the patients was 60.8 ± 12.3 years, and 85.4% were male. During the study period, 96.1% died, and median survival duration was 4.0 months. In multivariate analysis, Child-Pugh class, number and size of tumors, presence of vascular or bile duct invasion, lung or bone metastasis, serum AFP, and primary anti-HCC treatment were associated with survival. We constructed a model for survival prediction based on the relevant variables, which is available online (https://metastatic-hcc.onrender.com/form). Our model demonstrated high performance, with areas under the receiver operating characteristic curves of 0.778, 0.794, and 0.784 at 3, 6, and 12 months, respectively. Feature importance analysis indicated that the primary anti-HCC treatment had the highest importance. Conclusion: We developed a model to predict the survival of patients with HCC and extrahepatic metastasis, which demonstrated good discriminative ability. Our model would be helpful for personalized treatment and for improving the prognosis.

18p Deletion Syndrome Originating from Rare Unbalanced Whole-Arm Translocation between Chromosomes 13 and 18: A Case Report and Literature Review.

18p deletion (18p-) syndrome is a rare chromosome abnormality that has a wide range of phenotypes, with short stature, intellectual disability, and facial dysmorphism being the main clinical features. Here, we report the first case in Korea of a 16-year-old male adolescent with 18p- syndrome resulting from de novo unbalanced whole-arm translocation between chromosomes 13 and 18 (45, XY, der(13;18)(q10:q10)). Three rare clinical findings were discovered that had not been reported in the previous literature; morbid obesity without other hormonal disturbances, rib cage deformity leading to the direct compression of the liver, and lumbar spondylolisthesis at the L5-S1 level. This case expands the phenotypic spectrum of 18p- syndrome and highlights the importance of considering chromosomal analysis, since this syndrome can be easily overlooked in a clinical setting, especially without distinctive symptoms of other organs, due to its nonspecific but typical features of short stature and mild intellectual disability with a mildly dysmorphic face. Moreover, since not all cases of 18p- syndrome with unbalanced translocation (13;18) show the same phenotype, multidisciplinary examinations and follow-up seem to be important to monitor evolving and developing clinical manifestations and to predict prognosis in advance associated with the specific genes of 18p breakpoint regions.

Distributed source localization of epileptiform discharges in juvenile myoclonic epilepsy: Standardized low-resolution brain electromagnetic tomography (sLORETA) Study.

Juvenile myoclonic epilepsy (JME) is a common generalized epilepsy syndrome considered the prototype of idiopathic generalized epilepsy. To date, generalized and focal seizures have been the fundamental concepts for classifying seizure types. In several studies, focal features of JME have been reported predominantly in the frontal lobe. However, results in previous studies are inconsistent. Therefore, we investigated the origin of epileptiform discharges in JME. We performed electroencephalography source localization using a distributed model with standardized low-resolution brain electromagnetic tomography. In 20 patients with JME, standardized low-resolution brain electromagnetic tomography images corresponding to the midpoint of the ascending phase and the negative peak of epileptiform discharges were obtained from a total of 362 electroencephalography epochs (181 epochs at each timepoint). At the ascending phase, the maximal current source density was located in the frontal lobe (58.6%), followed by the parietal (26.5%) and occipital lobes (8.8%). At the negative peak, the maximal current source density was located in the frontal lobe (69.1%), followed by the parietal (11.6%) and occipital lobes (9.4%). In the ascending phase, 41.4% of discharges were located outside the frontal lobe, and 30.9% were in the negative peak. Frontal predominance of epileptiform discharges was observed; however, source localization extending to various cortical regions also was identified. This widespread pattern was more prominent in the ascending phase (P = .038). The study results showed that JME includes widespread cortical regions over the frontal lobe. The current concept of generalized epilepsy and pathophysiology in JME needs further validation.

Current Pharmacologic Strategies for Treatment of Intractable Epilepsy in Children.

Epileptic encephalopathy (EE) is a devastating pediatric disease that features medically resistant seizures, which can contribute to global developmental delays. Despite technological advancements in genetics, the neurobiological mechanisms of EEs are not fully understood, leaving few therapeutic options for affected patients. In this review, we introduce the most common EEs in pediatrics (i.e., Ohtahara syndrome, Dravet syndrome, and Lennox-Gastaut syndrome) and their molecular mechanisms that cause excitation/inhibition imbalances. We then discuss some of the essential molecules that are frequently dysregulated in EEs. Specifically, we explore voltage-gated ion channels, synaptic transmission-related proteins, and ligand-gated ion channels in association with the pathophysiology of Ohtahara syndrome, Dravet syndrome, and Lennox-Gastaut syndrome. Finally, we review currently available antiepileptic drugs used to treat seizures in patients with EEs. Since these patients often fail to achieve seizure relief even with the combination therapy, further extensive research efforts to explore the involved molecular mechanisms will be required to develop new drugs for patients with intractable epilepsy.

Effectiveness of Chloral Hydrate on Brain MRI in Children with Developmental Delay/Intellectual Disability Comparing with Normal Intelligence: Single Tertiary Center Experience.

Neurodiagnostic investigation requirements are expanding for diagnostic and therapeutic purposes in children, especially in those with developmental delay/intellectual disability (DD/ID). Thus, determination of optimal sedatives to achieve successful sedation and immobility without further neurological compromise is important in children with DD/ID. The purpose of this study is to assess the effectiveness and adverse reactions of chloral hydrate (CH) for brain magnetic resonance imaging (B-MRI) in children with DD/ID compared to those with normal intelligence (NI). We performed a retrospective chart review of children aged from 1 day to 12 years who required elective sedation using CH for B-MRI. About 730 cases (415 with DD/ID and 315 with NI) of CH sedation were conducted for B-MRI. Children with DD/ID showed a higher failure rate (22%) than did those with NI (6%); additional CH and prolonged sedation time were required. There was no difference in incidence of adverse reactions between DD/ID and NI groups (p = 0.338). Older or heavier children with DD/ID (p = 0.036 and p = 0.013, respectively), as well as those diagnosed with epilepsy or neuropsychiatric disorders showed higher risk of sedation failure (p < 0.001 for each). In conclusion, CH was a suboptimal sedative drug for children with DD/ID compared with those with NI. Other alternative or supplementary sedatives should be taken into consideration especially for those vulnerable groups.

Comparative Efficacy of Levetiracetam for Epilepsy in School-Aged Children with Intellectual Disability and Normal Intelligence.

Choosing optimal anti-seizure medication (ASM) is very important in pediatric patients with epilepsy who attend school, especially children with an intellectual disability (ID). Levetiracetam (LEV) has proven to be an effective, safe, generally well-tolerated, broad-spectrum ASM in children. In the context of increasing use of LEV in school-aged children with epilepsy and ID, we evaluate relevant clinical data, including efficacy, safety, and tolerability in children with epilepsy and an intellectual disability (ID) or normal intelligence (NI). We performed a retrospective chart review of children and included 298 pediatric patients with epilepsy who were treated with LEV with NI (147) and ID (151). After 6 months, 96% of NI and 83% of ID subjects had a seizure reduction rate greater than 50% (p = 0.031). The tolerability of LEV was generally good, with 75% retention rates at 2 years in both groups and only minor side effects (under 15%). The retention rates of patients with NI and ID were 76% and 74%, respectively (p = 0.597). Thus, LEV showed considerable efficacy with minimal side effects and high retention rates and is an easily maintained and safe treatment option for pediatric epilepsy with ID. However, better-designed research studies are needed to clearly elucidate the efficacy and safety of LEV in children with epilepsy and ID.

Seroprevalence of Hepatitis A Virus in Pediatric Patients with Hematologic Malignancies after Chemotherapy and Hematopoietic Cell Transplantation.

This retrospective study was performed to determine the seroprevalence of hepatitis A virus (HAV) in children and adolescents with hematologic malignancies after the completion of chemotherapy and hematopoietic cell transplantation (HCT). Of 97 enrolled patients, 60 (61.9%) were seropositive for HAV. The seroprevalences in patients undergoing chemotherapy and HCT were 60.3% (41/68) and 65.5% (19/29), respectively (P = 0.628). No significant factors associated with seropositivity for HAV after chemotherapy and HCT were identified. Anti-HAV tests and HAV re-vaccinations can be considered in children and adolescents with underlying hematologic malignancies after chemotherapy and HCT based on the anti-HAV results.