Epilepsy in sulfite oxidase deficiency and related disorders: insights from neuroimaging and genetics.

Sulfite oxidase deficiency (SOD) and related disorders, especially molybdenum cofactor deficiency (MoCD), are a group of rare and severe neurometabolic disorders caused by gene mutations that affect the sulfur-containing amino acid catabolic pathway. These disorders are characterized by distinctive neuroimaging features such as diffuse cerebral atrophy, multicystic encephalomalacia, and ventriculomegaly in early infancy. These features are essential for early diagnosis and treatment. Moreover, the genetics of these disorders are complex but have been increasingly elucidated in the era of molecular medicine. Therefore, we reviewed 28 articles (published from January 1967 until October 2021) on SOD and MoCD, focusing on their neuroimaging and genetic aspects. We highlighted the differences between SOD and MoCD and other conditions that may mimic them, such as common neonatal hypoxic-ischemic encephalopathy and uncommon neonatal metabolic disorder (Leigh syndrome). We also summarized the current knowledge on the genetic mechanisms and the manifestation of seizure disorders of SOD and MoCD. In conclusion, if clinical, neuroimaging, and neuropathological findings suggest a possible SOD or related disorder; extensive molecular diagnostics should be performed to confirm the diagnosis.

A Single Center Observational Study of Spirometry Assessments in Children with Congenital Heart Disease after Surgery.

Background: Children with congenital heart disease (CHD) have impaired pulmonary function both before and after surgery; therefore, pulmonary function assessments are important and should be performed both before and after open-heart surgery. This study aimed to compare pulmonary function between variant pediatric CHD types after open-heart surgery via spirometry. Methods: In this retrospective study, the data for forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the ratio between FEV1 and FVC (FEV1/FVC) were collected from patients with CHD who underwent conventional spirometry between 2015 and 2017. Results: A total of 86 patients (55 males and 31 females, with a mean age of 13.24 ± 3.32 years) were enrolled in our study. The diagnosis of CHD included 27.9% with atrial septal defects, 19.8% with ventricular septal defects, 26.7% with tetralogy of Fallot, 7.0% with transposition of the great arteries, and 46.5% with other diagnoses. Abnormal lung function was identified by spirometry assessments after surgery. Spirometry was abnormal in 54.70% of patients: obstructive type in 29.06% of patients, restrictive type in 19.76% of patients, and mixed type in 5.81% of patients. More abnormal findings were found in patients who received the Fontan procedure (80.00% vs. 35.80%, p = 0.048). Conclusions: Developing novel therapies to optimize pulmonary function will be critical for improving clinical outcomes.

Kawasaki Disease May Increase the Risk of Subsequent Cerebrovascular Disease.

BACKGROUND: Previous epidemiological investigations examining the association between Kawasaki disease (KD) and cerebrovascular disease have had conflicting results. We analyzed the association between KD and cerebrovascular disease by conducting a population-based retrospective cohort study designed to investigate the hypothesis that KD could be a risk factor for subsequent cerebrovascular disease. METHODS: From the National Health Insurance Research Database of Taiwan, the data of children (aged 0-18 years old) with KD (n=8467) were collected. Starting with the first year of study observation (referred to as the baseline year), data was collected for each child with KD, and 4 non-KD patients matched for sex, urbanization level of residence, and parental occupation were randomly selected to form the non-KD cohort (n=33 868) for our analysis. For the period from January 1, 2000, to December 31, 2012, we calculated the follow-up person-years for each patient, which is the time from the index date to the diagnosis of cerebrovascular disease, death, or the end of 2012. Furthermore, we compared the incidence, the incidence rate ratio, and the 95% CI of cerebrovascular disease between the KD and non-KD cohorts. RESULTS: The overall cerebrovascular disease incidence rate was found to be 3.19-fold higher, which is significantly higher, in the KD cohort than in the non-KD cohort (14.73 versus 4.62 per 100 000 person-years), and the overall risk of cerebrovascular disease remained higher in the KD cohort (adjusted hazard ratio, 3.16 [95% CI, 1.46-6.85]). Furthermore, children aged <5 years showed a significantly higher risk of subsequent cerebrovascular disease in the KD cohort (adjusted hazard ratio, 3.14 [95% CI, 1.43-6.92]). CONCLUSIONS: This nationwide retrospective cohort study shows that KD may increase the risk of subsequent cerebrovascular disease, especially in those with KD aged <5 years old.

Incidence of epilepsy in children born prematurely and small for gestational age at term gestation: A population-based cohort study.

AIM: This study assessed the incidence of epilepsy in preterm infants and those small for gestational age (SGA) at term and identified risk factors associated with higher epilepsy incidence in these children. METHODS: We enrolled children (from 2000 to 2010) who were premature (n = 21 474) or SGA (n = 2206); we then included a matched control cohort (n = 94 720). Cox regression was used to assess the epilepsy risk in preterm and SGA children. To determine the associated factors for epilepsy, the preterm and SGA infants were divided into six groups according to the common complications related to brain development and were separated into three subgroups based on birthweight (BW). RESULTS: The cumulative incidence of epilepsy was significantly higher in preterm or SGA children than in the control group. The overall incidence densities (per 1000 person-years) of epilepsy were: 0.37 in the control, 2.96 in the preterm, 2.90 in the SGA, 15.9 in the preterm with cerebral haemorrhage, 14.6 in the SGA with cerebral haemorrhage, 6.92 in the preterm with asphyxia, 3.82 in the SGA with asphyxia, 14.3 in the preterm with congenital brain anomalies, and 25.4 in the SGA with congenital brain anomalies cohorts. Infants with BW < 1000 g had a higher incidence of epilepsy than those with BW ≥2500 g. CONCLUSIONS: Preterm and SGA infants had an increased risk of epilepsy in childhood, and the incidence of epilepsy increased with decreasing BW. Several perinatal factors (e.g. intracranial haemorrhage, birth asphyxia and congenital brain anomalies) are associated with a higher incidence of later epilepsy.

Heterogeneous neurodevelopmental disorders in children with Kawasaki disease: what is new today?

BACKGROUND: Kawasaki disease (KD) is a common vasculitis of childhood in East Asia. The complications of KD ascribed to long-term cardiovascular sequelae are considerably diverse. Although studies have investigated neurodevelopmental problems following KD in the past few decades, they have reported inconsistent conclusions. This study investigated potential epilepsy and associated neurodevelopmental disorders (NDDs) following KD in Taiwanese children. METHODS: We retrospectively analyzed the data of children aged < 18 years with clinically diagnosed KD from January 1, 2005, to December 31, 2015. These patients were followed up to estimate the prevalence of epilepsy and associated NDDs in comparison with the prevalence in general pediatric population in Taiwan and worldwide. RESULTS: A total of 612 patients with an average age of 1.6 years were included. The prevalence of associated NDDs was 16.8% (n = 103/612) in the study group, which consisted of epilepsy, intellectual disability (ID), autism spectrum disorders, Tourette syndrome (TS), attention deficit hyperactivity disorder, (ADHD), and others. Moreover, children with KD had a higher prevalence of epilepsy and TS in both Taiwan and worldwide (epilepsy: 2.61% in the KD group vs 0.33% in Taiwan and 0.05-0.8% in worldwide, p < 0.05; TS: 2.77% in the KD group vs 0.56% in Taiwan and 0.3-1% in worldwide, p < 0.05). The prevalence of ID, ADHD, and developmental language disorders was not significantly different between our study patients and those in Taiwan or worldwide. CONCLUSIONS: Results revealed a higher prevalence rate of NDDs, especially epilepsy and TS, in Taiwanese children with KD than in the general pediatric population in Taiwan. However, these NDDs could be heterogeneous. Children diagnosed with KD were followed up because they had a higher risk of heterogeneous NDDs.

Epileptic spasms in PPP1CB-associated Noonan-like syndrome: a case report with clinical and therapeutic implications.

BACKGROUND: Noonan syndrome-like disorder with loose anagen hair-2 (NSLH2) is an extremely rare disease caused by a heterozygous mutation in the PPP1CB gene on chromosome 2p23. The syndrome causes not only numerous dysmorphic features but also hypotonia, developmental delay, and even intellectual disability. We report the first case of NSLH2 in Asia and the 16th in the world. Moreover, the first case of PPP1CB-related infantile spasms. The clinical and therapeutic significance is outlined in this paper. CASE PRESENTATION: We found a male infant presented with severe intractable epileptic spasms. Although certain clinical features of somatic dysmorphism were noted, numerous laboratory and neuroimaging studies failed to identify the cause. To determine the underlying etiology, whole-exome sequencing was conducted. We identified a de novo heterozygous mutation, NM_206876.1: c.548A > C (p.Glu183Ala), in the PPP1CB gene. His seizures were almost refractory to conventional antiepileptic drugs but relative seizure control was eventually achieved with a ketogenic diet. CONCLUSION: This result expands the clinical spectrum of NSLH2 and strengthens the association between the PPP1CB gene and epileptic seizures. Furthermore, we suggest that the ketogenic diet can offer seizure reduction in particular drug-resistant epilepsy syndromes. Additional studies are warranted to clarify the pathogenic mechanisms underlying this PPP1CB mutation in epileptic seizures.

Demographic and clinical characteristics, seizure disorders, and antiepileptic drug usage in different types of corpus callosum disorders: a comparative study in children.

BACKGROUND: This study aimed to investigate the demographic and clinical characteristics, types of seizure disorders, and antiepileptic drug usage among individuals with different types of corpus callosum disorders. METHODS: A total of 73 individuals were included in the study and divided into three groups based on the type of corpus callosum abnormality: hypoplasia (H), agenesis (A), and dysgenesis (D). Demographic data, including gender and preterm birth, as well as clinical characteristics such as seizure disorders, attention deficit hyperactivity disorder (ADHD), severe developmental delay/intellectual disability, and other brain malformations, were analyzed. The types of seizure disorders and antiepileptic drugs used were also examined. RESULTS: The H group had the highest number of participants (n = 47), followed by the A group (n = 11) and the D group (n = 15). The A group had the highest percentage of males and preterm births, while the D group had the highest percentage of seizure disorders, other brain malformations, and severe developmental delay/intellectual disability. The A group also had the highest percentage of ADHD. Focal seizures were observed in all three groups, with the highest proportion in the A group. Focal impaired awareness seizures (FIAS) were present in all groups, with the highest proportion in the D group. Generalized tonic-clonic seizures (GTCS) were observed in all groups, with the highest proportion in the H group. Different types of antiepileptic drugs were used among the groups, with variations in usage rates for each drug. CONCLUSION: This study provided insights into the demographic and clinical characteristics, seizure disorders, and antiepileptic drug usage among individuals with different types of corpus callosum disorders. Significant differences were found between the groups, indicating the need for tailored management approaches. However, the study has limitations, including a small sample size and a cross-sectional design. Further research with larger sample sizes and longitudinal designs is warranted to validate these findings and explore the relationship between corpus callosum abnormality severity and clinical outcomes.

Insights into clinical phenotypes and treatment responses in a Small cohort of Taiwanese patients with SCN1A variants: A Preliminary study.

BACKGROUND: SCN1A channelopathy is the most well-known cause for epileptic encephalopathies and contributes to a wide phenotypic spectrum. The variable expressivity is troublesome for the interpretation of clinical significance and prognoses. To investigate the clinical manifestations, medications and outcomes of patients with SCN1A channelopathies, we conducted this observation retrospective study in Taiwan. METHODS: A cohort consisting of 16 patients (5 males and 11 females) from multiple centers with identified SCN1A variants was investigated and phenotypically relevant factors were recorded. The variants were identified using NGS and confirmed by Sanger sequencing. A panel of 90 epileptic-related genes was used to identify SCN1A variants and to evaluate some of the potential SCN1A modifier genes. RESULTS: The mean age of seizure onset was 10.4 months. Twelve of the sixteen patients (75%) had different degrees of neurocognitive sequela and psychobehavioral comorbidity in our cohort. Cognitive impairment was noted in all ten patients with Dravet syndrome (DS) and in two of the patients with non-DS phenotypes. A lower response rate to medications was also noted in patients with DS. Notably, a medication-specific tendency towards valproic acid (VPA), clobazam (CLB), and levetiracetam (LEV) was observed, revealing the effective pharmacotherapies for SCN1A-related seizures. An asymptomatic carrier with a reported pathogenic SCN1A variant was reviewed along with her monozygotic twin sister with DS. Nine novel SCN1A mutations are herein reported, eight of which being classified as pathogenic. CONCLUSION: Our study revealed unfavorable outcomes for patients with SCN1A variants. Some patients with SCN1A channelopathy showed specific responsiveness to the pharmacotherapies previously either recommended or contraindicated for these patients. Our study also expands the genotype and provides valuable prognostic insights in patients with SCN1A channelopathy.

Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the Caenorhabditis elegans Model.

Defective autophagy is one of the cellular hallmarks of Parkinson's disease (PD). Therefore, a therapeutic strategy could be a modest enhancement of autophagic activity in dopamine (DA) neurons to deal with the clearance of damaged mitochondria and abnormal protein aggregates. Syringin (SRG) is a phenolic glycoside derived from the root of Acanthopanax senticosus. It has antioxidant, anti-apoptotic, and anti-inflammatory properties. However, whether it has a preventive effect on PD remains unclear. The present study found that SRG reversed the increase in intracellular ROS-caused apoptosis in SH-SY5Y cells induced by neurotoxin 6-OHDA exposure. Likewise, in C. elegans, degeneration of DA neurons, DA-related food-sensitive behaviors, longevity, and accumulation of α-synuclein were also improved. Studies of neuroprotective mechanisms have shown that SRG can reverse the suppressed expression of SIRT1, Beclin-1, and other autophagy markers in 6-OHDA-exposed cells. Thus, these enhanced the formation of autophagic vacuoles and autophagy activity. This protective effect can be blocked by pretreatment with wortmannin (an autophagosome formation blocker) and bafilomycin A1 (an autophagosome-lysosome fusion blocker). In addition, 6-OHDA increases the acetylation of Beclin-1, leading to its inactivation. SRG can induce the expression of SIRT1 and promote the deacetylation of Beclin-1. Finally, we found that SRG reduced the 6-OHDA-induced expression of miR-34a targeting SIRT1. The overexpression of miR-34a mimic abolishes the neuroprotective ability of SRG. In conclusion, SRG induces autophagy via partially regulating the miR-34a/SIRT1/Beclin-1 axis to prevent 6-OHDA-induced apoptosis and α-synuclein accumulation. SRG has the opportunity to be established as a candidate agent for the prevention and cure of PD.

Interaction of the C9orf72-Amyotrophic Lateral Sclerosis-Related Proline-Arginine Dipeptide Repeat Protein with the RNA-Binding Protein NOVA1 Causes Decreased Expression of UNC13A Due to Enhanced Inclusion of Cryptic Exons, Which Is Reversed by Betulin Treatment.

C9orf72 mutations are the most common form of familial amyotrophic lateral sclerosis (C9-ALS). It causes the production of proline-arginine dipeptide repeat proteins (PR-DPRs) in motor neurons (MNs), leading to the molecular pathology characteristic of ALS. UNC13A is critical for maintaining the synaptic function of MNs. Most ALS patients have nuclear deletion of the splicing repressor TDP-43 in MNs, which causes inclusion of the cryptic exon (CE) of UNC13A mRNA, resulting in nonsense-mediated mRNA decay and reduced protein expression. Therefore, in this study, we explored the role of PR-DPR in CE inclusion of UNC13A mRNA. Our results showed that PR-DPR (PR50) induced CE inclusion and decreased the protein expression of UNC13A in human neuronal cell lines. We also identified an interaction between the RNA-binding protein NOVA1 and PR50 by yeast two-hybrid screening. NOVA1 expression is known to be reduced in patients with ALS. We found that knockdown of NOVA1 enhanced CE inclusion of UNC13A mRNA. Furthermore, the naturally occurring triterpene betulin can inhibit the interaction between NOVA1 and PR50, thus preventing CE inclusion of UNC13A mRNA and protein reduction in human neuronal cell lines. This study linked PR-DPR with CE inclusion of UNC13A mRNA and developed candidate therapeutic strategies for C9-ALS using betulin.

Glycine-Alanine Dipeptide Repeat Protein from C9-ALS Interacts with Sulfide Quinone Oxidoreductase (SQOR) to Induce the Activity of the NLRP3 Inflammasome in HMC3 Microglia: Irisflorentin Reverses This Interaction.

Amyotrophic lateral sclerosis (ALS) is a fatal rare disease of progressive degeneration of motor neurons. The most common genetic mutation in ALS is the hexanucleotide repeat expansion (HRE) located in the first intron of the C9orf72 gene (C9-ALS). HRE can produce dipeptide repeat proteins (DPRs) such as poly glycine-alanine (GA) in a repeat-associated non-ATG (RAN) translation. GA-DPR has been shown to be toxic to motor neurons in various biological models. However, its effects on microglia involved in C9-ALS have not been reported. Here, we show that GA-DPR (GA50) activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome in a human HMC3 microglia model. MCC950 (specific inhibitor of the NLRP3) treatment can abrogate this activity. Next, using yeast two-hybrid screening, we identified sulfide quinone oxidoreductase (SQOR) as a GA50 interacting protein. SQOR knockdown in HMC3 cells can significantly induce the activity of the NLRP3 inflammasome by upregulating the level of intracellular reactive oxygen species and the cytoplasmic escape of mitochondrial DNA. Furthermore, we obtained irisflorentin as an effective blocker of the interaction between SQOR and GA50, thus inhibiting NLRP3 inflammasome activity in GA50-expressing HMC3 cells. These results imply the association of GA-DPR, SQOR, and NLRP3 inflammasomes in microglia and establish a treatment strategy for C9-ALS with irisflorentin.

Genetic Testing in Children with Developmental and Epileptic Encephalopathies: A Review of Advances in Epilepsy Genomics.

Advances in disease-related gene discovery have led to tremendous innovations in the field of epilepsy genetics. Identification of genetic mutations that cause epileptic encephalopathies has opened new avenues for the development of targeted therapies. Clinical testing using extensive gene panels, exomes, and genomes is currently accessible and has resulted in higher rates of diagnosis and better comprehension of the disease mechanisms underlying the condition. Children with developmental disabilities have a higher risk of developing epilepsy. As our understanding of the mechanisms underlying encephalopathies and epilepsies improves, there may be greater potential to develop innovative therapies tailored to an individual's genotype. This article provides an overview of the significant progress in epilepsy genomics in recent years, with a focus on developmental and epileptic encephalopathies in children. The aim of this review is to enhance comprehension of the clinical utilization of genetic testing in this particular patient population. The development of effective and precise therapeutic strategies for epileptic encephalopathies may be facilitated by a comprehensive understanding of their molecular pathogenesis.

Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction.

Glioblastoma (GBM) is a primary brain tumor of unknown etiology. It is extremely aggressive, incurable and has a short average survival time for patients. Therefore, understanding the precise molecular mechanisms of this diseases is essential to establish effective treatments. In this study, we cloned and sequenced a splice variant of the hydroxysteroid 11-ß dehydrogenase 1 like gene (HSD11B1L) and named it HSD11B1L-181. HSD11 B1L-181 was specifically expressed only in GBM cells. Overexpression of this variant can significantly promote the proliferation, migration and invasion of GBM cells. Knockdown of HSD11B1L-181 expression inhibited the oncogenic potential of GBM cells. Furthermore, we identified the direct interaction of parkin with HSD11B1L-181 by screening the GBM cDNA expression library via yeast two-hybrid. Parkin is an RBR E3 ubiquitin ligase whose mutations are associated with tumorigenesis. Small interfering RNA treatment of parkin enhanced the proliferative, migratory and invasive abilities of GBM. Finally, we found that the alkaloid peiminine from the bulbs of Fritillaria thunbergii Miq blocks the interaction between HSD11B1L-181 and parkin, thereby lessening carcinogenesis of GBM. We further confirmed the potential of peiminine to prevent GBM in cellular, ectopic and orthotopic xenograft mouse models. Taken together, these findings not only provide insight into GBM, but also present an opportunity for future GBM treatment.

Genetic factors and the risk of drug-resistant epilepsy in young children with epilepsy and neurodevelopment disability: A prospective study and updated meta-analysis.

ABSTRACT: Drug-resistant epilepsy (DRE) affects 7% to 20% of children with epilepsy. Although some risk factors for DRE have been identified, the results have not been consistent. Moreover, data regarding the risk factors for epilepsy and its seizure outcome in the first 2 years of life are limited.We analyzed data for children aged 0 to 2 years with epilepsy and neurodevelopmental disability from January, 2013, through December, 2017. These patients were followed up to compare the risk of DRE in patients with genetic defect (genetic group) with that without genetic defect (nongenetic group). Additionally, we conducted a meta-analysis to identify the pooled prevalence of genetic factors in children with DRE.A total of 96 patients were enrolled. A total of 68 patients were enrolled in the nongenetic group, whereas 28 patients were enrolled in the genetic group. The overall DRE risk in the genetic group was 6.5 times (95% confidence interval [CI], 2.15-19.6; p = 0.03) higher than that in the nongenetic group. Separately, a total of 1308 DRE patients were participated in the meta-analysis. The pooled prevalence of these patients with genetic factors was 22.8% (95% CI 17.4-29.3).The genetic defect plays a crucial role in the development of DRE in younger children with epilepsy and neurodevelopmental disability. The results can serve as a reference for further studies of epilepsy panel design and may also assist in the development of improved treatments and prevention strategies for DRE.

Amplitude Integrated Electroencephalography and Continuous Electroencephalography Monitoring Is Crucial in High-Risk Infants and Their Findings Correlate With Neurodevelopmental Outcomes.

Background: To evaluate seizure diagnosis in sick infants in the neonatal intensive care unit (NICU) based on electroencephalography (EEG) monitoring combined with amplitude integrated electroencephalography (aEEG). Methods: We retrospectively reviewed EEG and aEEG findings and determined their correlations with neurodevelopmental outcomes at the age of >1 year in 65 patients with diagnosed seizures, encephalopathy, or both. Results: Seizure identification rate was 43.1%. The rate in nonstructural groups (hypocalcemic, hypoglycemic, and genetic seizures) was 71.4%, which was higher (p < 0.05) than the rate of 35.3% of structural brain lesion group [hypoxic-ischemic encephalopathy (HIE) and congenital brain structural malformation]. The aEEG background correlating with neurodevelopmental outcomes had 70.0% positive prediction value (PPV), 65.5%% negative prediction value (NPV), 67.7% specificity, and 67.9% sensitivity (p < 0.005). The aEEG background strongly (PPV, 93.8%; p < 0.005) correlated with the outcomes in HIE. For genetic seizures, the detected rate was high. The ictal recordings for the nonstructural seizures revealed downflected on the aEEG background initially, which differed from the structural lesion. Conclusions: EEG monitoring combined with aEEG can detect seizures, facilitating early treatment. EEG changes during seizures could exhibit delta-theta waves with or without clinical seizures in patients with brain lesions. In non-structural etiologies (hypocalcemic and KCNQ2 seizures), aEEG initially exhibited lower background during seizures that could aid in differentiating these EEG changes from those of other etiologies. The aEEG background was correlated with neurodevelopmental outcome and exhibited high PPV but not NPV in neonatal HIE.

Is Preterm Birth a Risk Factor for Subsequent Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder in Children with Febrile Seizure?-A Retrospective Study.

Febrile seizure (FS) is the most prevalent childhood seizure; it is significantly related to subsequent epilepsy and has possible links to childhood neurodevelopmental disorders. Separately, premature births are believed to increase the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Therefore, this study investigated whether preterm birth is a risk factor for subsequent epilepsy, ASD, and ADHD in children with FS. We retrospectively collected data for children aged < 5 years with FS from 1 January 2005, to 31 December 2013. We divided these children into two groups-the premature birth group and the full-term group-and compared their incidence rates of epilepsy, ASD and ADHD. The data of 426 patients with history of febrile convulsion were retrospectively collected. The premature birth group (FS+/preterm+) had 108 patients and the full-term group (FS+/preterm-) had 318 patients. The overall epilepsy risk in the FS+/preterm+ group was higher than in the FS+/preterm- group (odds ratio [OR], 2.52; 95% confidence interval [CI], 1.14-5.58; p = 0.02). The overall risk of ADHD in the FS+/preterm+ group was higher than that in the FS+/preterm- group (OR, 6.41; 95% CI, 3.39-12.09; p = 0.0001). In addition, children with FS+/preterm+ had 16.9 times (95% CI, 4.79-59.7; p = 0.0001) higher odds of having ASD compared with those with FS+/preterm-. Preterm birth may be a risk factor for subsequent epilepsy, ASD and ADHD in children with FS.

Cytomegalovirus Infection in Infancy May Increase the Risk of Subsequent Epilepsy and Autism Spectrum Disorder in Childhood.

Cytomegalovirus (CMV) is a ubiquitous virus, and CMV-associated diseases range from mild illness in immunologically normal hosts to life-threatening diseases in newborns and immunocompromised children. This study investigated the association between childhood CMV infection and subsequent epilepsy or neurodevelopmental disorders, attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). A retrospective analysis was performed on data for 69 children with confirmed CMV infections (CMV infection group) and 292 patients with other infections (control group) between 1 January 2006 to 31 December 2012. The results indicated that the CMV infection group had a higher risk of epilepsy in comparison to the control (odds ratio (OR), 16.4; 95% CI (confidence interval), 3.32-80.7; p = 0.001). Epilepsy risk increased in younger children (age 0-2) with CMV infection when compared to the control group (OR, 32.6; 95% CI, 3.84-276; p = 0.001). The ASD risk was also determined to be higher in the CMV infection group (OR, 17.9; 95% CI, 1.96-162; p = 0.01). The ADHD risk between the groups was not significant. This study suggests that CMV infection in infancy may increase the risk of subsequent epilepsy and ASD, especially in infants younger than 2 years, but is not associated with ADHD.

Lamotrigine Induced DRESS Syndrome in a Child: A Case Report and Literature Review.

Lamotrigine is an important anticonvulsant drug. Its use, however, has been limited by the risk of potentially life-threatening dermatological reactions, such as a drug reaction with eosinophilia and systemic symptoms (DRESS). Here, we report the case of a 7-year-6-month-old girl with a history of epilepsy who developed a skin rash with dyspnoea after 2 weeks of lamotrigine treatment, with DRESS ultimately being diagnosed. After discontinuation of the offending drug and the initiation of systemic glucocorticosteroids, the DRESS symptoms were relieved and the patient was discharged in a stable condition. Anticonvulsant drugs such as lamotrigine are among the factors that induce DRESS in children. When a patient displays skin rash and systemic organ involvement following the initiation of an anticonvulsant drug, DRESS should not be overlooked as a diagnosis, and immunosuppressant drugs should be considered as an option for treating DRESS patients.

Polysomnography Is an Important Method for Diagnosing Pediatric Sleep Problems: Experience of One Children's Hospital.

In this study, we collected and analyzed polysomnography (PSG) data to investigate the value of PSG in diagnosing sleep problems in children. The results of PSG studies of children (<18 years old) with sleep problems conducted from April 2015 to May 2017 at a children's hospital in Taiwan were collected and analyzed retrospectively. Data for 310 patients (209 males and 101 females) who underwent PSG were collected. The final diagnoses were as follows: obstructive sleep apnea in 159 (51.3%), snoring in 81 (26.4%), limb movement sleep disorder in 25 (8.1%), hypersomnias in 12 (3.9%), central apnea in 8 (2.9%), enuresis in 7 (2.3%), bruxism in 5 (1.6%), sleep terrors in 5 (1.6%), narcolepsy in 3 (1.0%), sleep seizures in 3 (1.0%), sleep walking in 1 (0.3%), and insomnia in 1 (0.3%). PSG may help detect significant sleep-related problems in children and is useful for making therapeutic decisions regarding children. Obstructive sleep apnea syndrome (OSAS) was the primary sleep problem for most of the children (51.3%); however, only 7.4% of them underwent surgery for OSAS. We therefore suggest that children with sleep problems should undergo PSG.

Comparison of severe pediatric complicated influenza patients with and without neurological involvement.

ABSTRACT: Although influenza is generally an acute, self-limited, and uncomplicated disease in healthy children, it can result in severe morbidity and mortality. The objectives of this study were to analyze and compare the clinical features and outcome of severe pediatric influenza with and without central nervous system (CNS) involvement.We conducted a retrospective observational study of children admitted to the pediatric intensive care unit (PICU) of China Medical University Children's Hospital in Taiwan with a confirmed diagnosis of influenza. The demographic data, clinical and laboratory presentations, therapeutic strategies, and neurodevelopmental outcomes for these patients were analyzed. Furthermore, comparison of patients with and without CNS involvement was conducted.A total of 32 children with severe influenza were admitted during the study periods. Sixteen children were categorized as the non-CNS (nCNS) group and 16 children were categorized as the CNS group. Nine of them had underlying disease. The most common complication in the nCNS group was acute respiratory distress syndrome, (n = 8/16), followed by pneumonia (n = 7/16, 44%). In the CNS group, the most lethal complication was acute necrotizing encephalopathy (n = 3/16) which led to 3 deaths. The overall mortality rate was higher in the CNS group (n = 6) than in the nCNS group (n = 1) (37.5% vs 6.25%, P = .03).The mortality rate of severe complicated influenza was significantly higher with CNS involvement. Children with primary cardiopulmonary abnormalities were at high risk of developing severe complicated influenza, while previously healthy children exhibited risk for influenza-associated encephalitis/encephalopathy.