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Background: Vagus nerve stimulation (VNS) is used as an add-on treatment for epilepsy. This study aimed to use Taiwanese nationwide registry data to analyze the therapeutic effects of VNS in children with refractory epilepsy (RE) and try to explore predictive factors of VNS treatment effectiveness. Methods: This retrospective study collected data from December 2007 to December 2014. Patient variables included gender, age, VNS implantation date, epilepsy duration, seizure frequency, seizure type, etiology, and antiepileptic drug (AED) history. We divided patients into three groups: Group I as seizure frequency >80 times per month, Group II as seizure frequency 24–80 times per month, and Group III as seizure frequency

Background: Anomalous left coronary artery from the pulmonary artery (ALCAPA), a very rare congenital cardiac anomaly, is associated with a high mortality rate among infants who are not diagnosed or treated in a timely manner. Surgical intervention with the reconstruction for a two-coronary-system circulation is the main treatment; however, there have been very few reported cases from Taiwan. In this study, we aim to describe the clinical manifestations, diagnostic methods, surgery types, and surgical outcomes in patients with ALCAPA from a single Taiwanese medical center. Methods: We retrospectively reviewed patients diagnosed with ALCAPA who underwent surgery at our institution between January 2001 and October 2018. Clinical presentations, noninvasive and invasive study results, surgical methods, and postoperative follow-up results were assessed from medical records. Moreover, literature on this particular cardiovascular anomaly was reviewed. Results: The study included 6 patients (5 children and 1 adult). The diagnosis was confirmed using cardiac catheterization and coronary angiography in four patients and only echocardiography in two patients. All patients underwent surgical correction and survived. Four patients showed improvements in left ventricular function and mitral regurgitation (MR). Conclusion: Early diagnosis and timely surgical intervention could avoid mortality regardless of the method of operation. ALCAPA can be definitively diagnosed using noninvasive echocardiography. Both left ventricular systolic function and mitral insufficiency could improve after the surgical intervention in pediatric patients. Repair or replacement of the mitral valve could be reserved for persistent MR complicated with congestive heart failure, particularly in patients who received the initial operation beyond infancy.

Type 1 diabetes (T1D) is caused by the destruction of β cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective treatment for T1D. However, the survival of islet grafts is often disrupted by recurrent autoimmunity. Alpha-lipoic acid (ALA) has been reported to have immunomodulatory effects and, therefore, may have therapeutic potential in the treatment of T1D. In this study, we investigated the therapeutic potential of ALA in autoimmunity inhibition. We treated non-obese diabetic (NOD) mice with spontaneous diabetes and islet-transplantation mice with ALA. The onset of diabetes was decreased and survival of the islet grafts was extended. The populations of Th1 cells decreased, and regulatory T cells (Tregs) increased in ALA-treated mice. The in vitro Treg differentiation was significantly increased by treatment with ALA. The adoptive transfer of ALA-differentiated Tregs into NOD recipients improved the outcome of the islet grafts. Our results showed that in vivo ALA treatment suppressed spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Tregs. Our study also demonstrated the therapeutic potential of ALA in Treg-based cell therapies and islet transplantation used in the treatment of T1D.

Dravet syndrome (DS) is an uncommon epilepsy syndrome that may negatively affect the patients and their caregivers. However, reliable and valid measures of its impact on caregivers and the characteristics of patients with DS in Taiwan are lacking. This study aimed to describe the characteristics of patients with DS and concerns of their caregivers and establish a baseline frequency of disease characteristics using a cross-sectional survey in Taiwan. We assessed the caregivers of patients with DS using an online anonymous questionnaire. The seizure frequency decreased with age, although lacking statistical significance. Vaccines show no influence on the condition of patients with DS. Our findings revealed the highest impact on the domains affecting the caregivers’ daily life, including additional household tasks, symptom observation, further medical plan, and financial issues. Caregivers also expressed concerns regarding the lack of independence/constant care, seizure control, speech/communication, and impacts on siblings because of long-term care of the patients in parents’ absence. Our findings highlight the significant effects of caring for a child with DS on the lives of their caregivers in Taiwan; these findings will help raise awareness regarding the needs of these families. Furthermore, we discussed the possible pathophysiological mechanisms of associated comorbidities.

Neuromyelitis optica (NMO) is recognized as a different CNS autoimmune disease from multiple sclerosis (MS). Whether NMO-IgG contributes directly to the pathogenesis of NMO or is just a serologic marker of autoimmune responses of the disease needs to be clarified. We created MOG-induced experimental autoimmune encephalomyelitis (EAE) mice by passively transferring NMO-IgG to model the pathogenic findings in NMO patients. The mice were divided into three groups and administered intrathecal PBS, human complement with IgG from normal subjects, or IgG from AQP4(+) patients on days 8 and 11 after immunization. The EAE scores of EAE mice with intrathecal NMO-IgG injection were significantly elevated 14 days post-immunization. All of the mice were sacrificed for brain and spinal cord pathology analysis on day 21 post-immunization. Compared to mice given normal human IgG, EAE mice injected with NMO-IgG had markedly decreased AQP4 and glial fibrillary acidic protein (GFAP) expression and fluorescent intensity in the brain and spinal cord but more scattered deposition of complement (C9neo). Thus, our studies not only support the pathogenic role of NMO-IgG with complement in NMO disease but also provide a platform for the development of future therapeutics.

Rationale: Neuromyelitis optica spectrum disorders (NMOSD) is a rare autoimmune disease predominantly involving optic nerves and spinal cord, and possible comorbidities including syndrome of inappropriate antidiuretic hormone secretion or urinary complication. We reported a young girl diagnosed with NMOSD presented with refractory hyponatremia, acute urine retention, and general weakness. Clinical symptoms improved gradually after receiving intravenous immunoglobulin, high-dose methylprednisolone, and plasmapheresis. NMOSD should be kept in mind in adolescence with acute urine retention, intermittent fever, and hyponatremia. Patient concerns: A 15-year-old girl admitted to our hospital due to no urination for 2 days. Diagnosis: Aquaporin-4 antibodies were detected showing positive both in serum and cerebrospinal fluid. Long transverse myelitis in cervical and thoracic spinal cord and optic neuritis was revealed in magnetic resonance imaging. Interventions: Intravenous immunoglobulin 2 g/kg was infused totally in 4 days, and methylprednisolone pulse therapy was subsequently followed in 5 days; followed by 5 courses of plasmapheresis a week later. Outcomes: Her muscle power, syndrome of inappropriate antidiuretic hormone secretion condition, and urinary function were all improved after immune-modulated treatment course; NMOSD relapsed twice within the first year after diagnosis, however no relapse of NMOSD in the subsequent 1 year. Lessons: To the best of our knowledge, this was the first childhood case of NMO accompanied by refractory hyponatremia in the reported literature. In childhood cases presenting with refractory hyponatremia and limb weakness, NMO or NMOSD should be considered possible diagnoses despite their rarity in pediatric cases.

Bacillus cereus is an aerobic Gram-positive, spore-forming, rod-shaped bacterium that is responsible for foodborne illnesses. We report on a 15-year-old girl with B-cell acute lymphoblastic leukemia, who fell into a somnolent state after presenting with a 12-hour history of fever, muscle soreness, myalgia in both calves, sore throat, and vomiting. Fulminant septicemic syndrome caused by B. cereus was finally identified. The aim of this work is the introduction of B. cereus as a differential diagnosis of sepsis in patients with acute leukemia in induction chemotherapy, to prevent delayed treatment.

Child abuse affects children physiologically and psychologically, increasing the risk of future psychiatric disorders.To assess whether child abuse victims have a higher incidence of future psychiatric disorders or substance abuse.The participants consisted of a nationwide, population-based cohort selected in accordance with the Taiwan National Health Insurance Research Database. All children were enrolled between 2000 and 2015.This was a retrospective study with a matched-cohort design. Children who experienced child abuse were identified using International Classification of Disease codes and compared with children who had not experienced child abuse by measuring rates of anxiety disorders, depressive disorders, bipolar disorders, sleep disorders, posttraumatic stress disorder/acute stress disorder, eating disorders, substance-related disorders (alcohol use disorder and illicit drug use disorder), psychotic disorders, and organic mental disorders.The psychiatric disorder risk was significantly higher in victims of child abuse than in controls (adjusted hazard ratio, 2.15; 95 % confidence interval, 1.92-2.40; P0.001). The Kaplan-Meier analysis revealed a significantly higher 15-year cumulative incidence of psychiatric disorders among child abuse victims than among controls (394.57 vs. 317.56 events per 100,000 person-years; log-rank test, P 0.001).In Taiwan, child abuse is associated with increased psychiatric disorder and substance abuse risk. Individuals involved in caring for abused children, including family members, pediatricians, nurses, and social workers, as well as policy makers, should be aware of this risk. Early referral of child abuse victims to pediatric psychiatrists may help detect high-risk cases and facilitate early intervention.

Obesity may increase the risk of infection, but the association between obesity and febrile urinary tract infection (fUTI) is controversial. Although the prevalence of infant and childhood obesity has been increasing worldwide, the results of previous investigations on the association with urinary tract infection (UTI) are conflicting. The purpose of this study was to evaluate the relationship between overweight and obesity and UTI in febrile children. The study reviewed medical records of a consecutive series of 472 children

Objectives Refractory epilepsy (RE) is frequently associated with neuropsychological impairment in children and may disrupt their social development. Vagus nerve stimulation (VNS) had been reported to have beneficial effects on behavioral outcomes. The aim of this study was to compare Parenting Stress Index (PSI) scores before and after VNS device implantation in children with RE, especially those who experienced seizure frequency reduction. Methods We conducted a one-group pretest–posttest study in school age children with RE. Seizure frequency and PSI were recorded at 12 months after VNS device implantation. Results Treatment with VNS was significantly associated with reduced seizure frequency and parental stress as measured by PSI. Factors contributing to seizure frequency included idiopathic/cryptogenic etiology and neurobehavioral comorbidities. In children with reduced seizure frequency, statistically significant improvements in the child domain of the PSI on the subscales of mood and reinforces parent were found. In the parent domain, the scores for social isolation were reduced. Conclusions Treatment with VNS was significantly associated with reduced seizure frequency and improved PSI scores, especially within the child domain on the mood and reinforces parent subscales. These findings suggest that VNS reduced not only seizure frequency but also the psychological burden on children with RE.

Background/Purpose To retrospectively analyze the clinical manifestations of Mycoplasma pneumoniae ( M. pneumoniae )-associated encephalopathy in pediatric patients. Methods Pediatric patients with positive serum anti- M. pneumoniae immunoglobulin M (IgM) were enrolled in this study. Clinical signs and symptoms, laboratory data, neuroimaging findings, and electrophysiological data were reviewed. Results Of 1000 patients identified, 11 (1.1%; male:female ratio = 7:4) had encephalopathy and were admitted to the pediatric intensive care unit. Clinical presentation included fever, symptoms of respiratory illness, and gastrointestinal upset. Neurological symptoms included altered consciousness, seizures, coma, focal neurological signs, and personality change. Neuroimaging and electroencephalographic findings were non-specific. Specimens of cerebrospinal fluid (CSF) for M. pneumoniae polymerase chain reaction (PCR) were negative. Higher M. pneumoniae IgM titers and longer intervals between respiratory and CNS manifestations were associated with worse outcomes. Conclusion Clinical manifestations of M. pneumoniae -associated encephalopathy were variable. Diagnosis of M. pneumoniae encephalopathy should not rely on CSF detection of M. pneumoniae by PCR. M. pneumoniae IgM titers and intervals between respiratory and CNS manifestations might be possibly related to the prognosis of patients with M. pneumoniae -associated encephalopathy.

Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development–Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period ( P = .18 > .05). The cognitive development was positively correlated with motor development ( r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age.

Cauda equina syndrome (CES) in children is very rare and can permanently disable. A remitted intracranial germinoma depositing on the spinal cord, leading to CES, has never been reported. We discuss the case of a 10-year-old girl who presented with sudden ataxia, low back pain, sensory deficits of the left lower extremity, and difficulty urinating and defecating 7 months after totally remitted intracranial germinoma postintracranial surgery and cranial irradiation. Magnetic resonance imaging (MRI) of the brain and spine showed multiple intradural extramedullary homogeneous masses from the cervical to lumbar levels, compressing the conus medullaris and cauda equina. After emergent craniospinal irradiation, the patient's neurologic symptoms dramatically subsided. A remitted intracranial germinoma depositing on her spinal cord could be the cause of CES. Early identification and a proper craniospinal irradiation may halt the progression of symptoms.

The immunologic interaction between the fetus and the mother is a paradoxical communication that is regulated by fetal antigen presentation and/or by recognition of and reaction to these antigens by the maternal immune system. There have been significant advances in understanding of abnormalities in the maternal-fetal immunologic relationship in the placental bed that can lead to pregnancy disorders. Moreover, immunologic recognition of pregnancy is vital for the maintenance of gestation, and inadequate recognition of fetal antigens may cause abortion. In this paper, we illustrate the complex immunologic aspects of human reproduction in terms of the role of human leukocyte antigen (HLA), immune cells, cytokines and chemokines, and the balance of immunity in pregnancy. In addition, we review the immunologic processes of human reproduction and the current immunologic therapeutic strategies for pathological disorders of pregnancy.

Dandy–Walker syndrome (DWS) is a congenital brain malformation involving the cerebellum and fourth ventricle. We report a 6-month-old girl with DWS presenting an initially normal ventricular system and mild cyst-like lesion over the posterior fossa as assessed by postnatal brain sonography. However, symptoms and signs of increased intracranial cerebral pressure in terms of frequent vomiting and tense anterior fontanel developed, and these were associated with mild hypotonia and poor neck support, and upward-gaze palsy at the age of 6 months. Magnetic resonance imaging revealed a huge cystic lesion of the fourth ventricle, which filled the posterior fossa and ventricular dilatation. The tentorium was progressively displaced upward by the cyst. A nearly complete agenesis of the cerebellar vermis was also confirmed. After a successful endoscopic third ventriculostomy, a series of brain magnetic resonance imaging scans, taken during a follow-up survey, showed normal lateral and third ventricles. Consequently, symptoms of intracranial cerebral pressure resolved, and a developmental milestone was achieved. In conclusion, DWS can be confirmed postpartum, and endoscopic third ventriculostomy was found to be a preferential operative procedure for DWS with hydrocephalus. It may be effective for patients younger than 1 year.

Background and Objective: It was the aim of this study to determine the prevalence of anti-aquaporin 4 antibody (anti-AQP4 Ab) and long spinal cord lesions in neuromyelitis optica (NMO) and multiple sclerosis (MS) patients in Taiwan. Asia has a relatively high rate of NMO compared with MS patients. Anti-AQP4 Ab is an important marker for NMO worldwide, but serological data and clinical profiles of NMO patients in Taiwan have not been reported. Methods: This retrospective study compared the clinical symptoms, demographics, spinal cord lesion length and AQP4 Ab status of 34 patients with NMO with 34 patients diagnosed with conventional MS. Results: Our NMO patients were predominantly middle-aged women (median age 45 years), exhibited many relapses (1.0/year) and displayed a higher Expanded Disability Status Scale score (4.75) than conventional MS patients. NMO patients exhibited long spinal cord lesions as detected by MRI. Forty-one percent of the NMO patients had detectable anti-AQP4 Ab. The Expanded Disability Status Scale score was significantly higher in AQP4 Ab– NMO patients. Conclusion: The prevalence of AQP4 Ab in a Taiwanese NMO group was 41%. Long spinal cord lesions and detection of AQP4 Ab helped to differentiate NMO patients from MS patients. Long spinal cord lesions with the anti-AQP4 Ab test may allow for an earlier diagnosis of NMO and improve therapeutic decisions.

Background Staphylococcal scarlet fever (SSF), a rare disease, was first described in 1900. The clinical features and outcomes in children with SSF caused by Panton-Valentine leukocidin (PVL)-positive and PVL-negative Staphylococcus aureus strains have not been compared prospectively. Methods The demographic data, selected clinical features, laboratory values, and outcomes for 49 consecutive children with community-acquired S. aureus SSF prospectively identified during an 11-year period were collected for analysis. Results The male-to-female ratio was 1.88, and the median age of the patients was 37 months. Cutaneous abscesses predominated among children with SSF. Methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) caused SSF in 26 and 23 children, respectively. Twenty-four isolates had results that were positive for PVL (5 MSSA and 19 MRSA isolates), and 25 had results that were negative for PVL (21 MSSA and 4 MRSA isolates). Polymerase chain reaction revealed that most (92%) contained only staphylococcal enterotoxin B (23 MSSA and 22 MRSA isolates). By multivariate analysis, children with PVL-positive isolates had significantly larger abscess sizes, higher white blood cell counts, higher C-reactive protein levels, and longer durations of fever, generalized scarlatiniform rashes, and hospital stays. Most (17 isolates; 89%) of the 19 PVL-positive MRSA isolates carried the staphylococcal cassette chromosome mec V(T) and all were multilocus sequence type 59. Conclusion SSF caused by PVL-positive S. aureus strains were associated with more-exacerbated skin manifestations and a greater systemic inflammatory response, compared with those cases caused by PVL-negative S. aureus. Clinical improvement after incision and drainage was achieved for most children with SSF caused by PVL-positive MRSA strains, despite treatment with an ineffective antibiotic.

Membranous nephropathy is an autoimmune-mediated glomerulonephritis and a major cause of nephrotic syndrome. We studied the kinetics of adaptive immunity in the pathogenesis of membranous nephropathy in T1/T2 double transgenic mice (T1/T2 TG mice) that express human Thy1 protein under the control of interferon-gamma (INF-gamma) and mouse Thy1.1 protein under the control of interleukin (IL)-4. Nephropathy was induced by cationic bovine serum albumin. We found that splenocytes expressed a progressive Th2 response and a subsequent compensatory T-helper 1 (Th1) response, with a gradual augmentation of IL-4-producing Th2 cells and INF-gamma-producing Th1 cells. Increased Th2 marker expression was seen in peripheral blood and kidney cells, with the immunoglobulin G1 (IgG1) antibody isotype predominant in the serum and kidneys. We found that CD8+ T cells contribute more to the augmented INF-gamma production than CD4+ T cells. Moreover, CD19+ B cells demonstrated a greater production of IL-4 than the CD4+ T cells. Cytokine-related gene expression in kidneys and splenocytes showed an upregulation of proinflammatory Th1 and Th2 cytokines. Th2 cells but not Th1 cells were significantly correlated with serum cholesterol and proteinuria. Our study shows that both peripheral and renal immune reactions are strongly polarized toward Th2-type immune responses during the course of membranous nephropathy. The T1/T2 mouse model may help decipher the kinetic changes of adaptive immunity in glomerulonephritis.

Background Children with longstanding use of antiepileptic drugs (AEDs) are susceptible to developing low bone mineral density and an increased fracture risk. However, the literature regarding the effects of AEDs on growth in epileptic children is limited. The aim of this study was to investigate the potential effects of valproate (VPA) and/or oxcarbazepine (OXC) therapy on growth velocity and bone metabolism. Methods Seventy-three ambulatory children (40 boys and 33 girls) with epilepsy, aged between 1 and 18 years (mean age 9.8 ± 4.1 years), were evaluated for growth velocity before and for 1 year after VPA and/or OXC treatment. The bone resorption marker serum tartrate-resistant acid phosphatase 5b (TRAcP5b) and the bone formation marker serum bone-specific alkaline phosphatase (BAP) were measured post-AEDs therapy for 1 year. Results The difference in growth velocity (ΔHt) and body weight change (ΔWt) between pre- and post-AEDs treatment were -1.0 ± 2.8 cm/year (P

With limited near-field resolution and accessible acoustic windows, sonography has not been advocated for assessing central nervous system injuries in the shaken-baby syndrome. Our purpose was to correlate high-resolution ultrasonographic characteristics of central nervous system injuries in whiplash injuries and the shaken-baby-syndrome with MRI and CT. Ultrasonographic images of 13 infants, aged 2-12 months, with whiplash or shaking cranial trauma were reviewed and compared with MRI in 10 and CT in 10. Five patients had serial ultrasonography and MRI or CT follow-up from 1 to 4 months after the initial injury. With ultrasonography we identified 20 subdural haematomas. MRI and CT in 15 of these showed that four were hyperechoic in the acute stage, three were mildly echogenic in the subacute stage, and that one subacute and seven chronic lesions were echo-free. Five patients had acute focal or diffuse echogenic cortical oedema which evolved into subacute subcortical hyperechoic haemorrhage in four, and well-defined chronic sonolucent cystic or noncystic encephalomalacia was seen at follow-up in two. Using ultrasonography we were unable to detect two posterior cranial fossa subdural haematomas or subarachnoid haemorrhage in the basal cisterns in three cases, but did show blood in the interhemispheric cistern and convexity sulci in two. U1-trasonography has limitations in demonstrating abnormalities remote from the high cerebral convexities but may be a useful adjunct to CT and MRI in monitoring the progression of central nervous system injuries in infants receiving intensive care.

Medulloblastoma is one of the notorious CNS malignancies for subtle and atypical clinical presentations, causing rapid neurological deterioration and death, especially in pediatric patients. The delay in diagnosis leads to painful remorse, conflicts, and lawsuits for parents and medical staff.We report a 2 year old girl with initial presentation of febrile pyuria. Soon after admission, a generalized clonic-tonic seizure attacked to her and led to an impression of febrile convulsion. However, an unusual postical slowness of pupils to light stimulation propelled a further investigation. A contrast enhanced brain computer tomography (CT) unexpectedly showed a mass occupied the fourth ventricle resulting in obstructive hydrocephalus and compressed adjacent brain stem and cerebellum. The disease rapidly progressed and she died 18 hours after an emergent decompression with extraventricular drainage (EVD) installation. Cytology of cerebrospinal fluid proved medulloblastoma.This case report highlights the importance of clinical suspicion, such as a trivial but unusual presentation, a lagged pupil response to light stimulation. A brain CT scan should be done to rule out any possibility of an organic lesion. Close monitor is required in order to catch and treat medulloblastoma early. However, once discovered, the cancer has spread.

Background Allergic disorders have increased substantially in recent years. Asthma is characterized by airway damage and remodeling. Reprogramming induced pluripotent stem cells (iPSCs) from adult somatic cells transfected by Oct-4/Sox-2/Klf-4, but not c-Myc, has shown the potential of embryonic-like cells. These cells have potential for multilineage differentiation and provide a resource for stem cell-based utility. However, the therapeutic potential of iPSCs without c-Myc (iPSC-w/o-c-Myc) in allergic diseases and airway hyperresponsiveness has not been investigated. The aim of this study was to evaluate the therapeutic effect of iPSC-w/o-c-Myc transplantation in a murine asthma model. Methods BALB/c mice were sensitized with alum-adsorbed ovalbumin (OVA) and then challenged with aerosolized OVA. Phosphate-buffered saline or iPSC-w/o-c-Myc was then intravenously injected after inhalation. Serum allergen-specific antibody levels, airway hyperresponsiveness, cytokine levels in spleen cells and bronchoalveolar lavage fluid (BALF), and cellular distribution in BALF were then examined. Results Treatment with iPSC-w/o-c-Myc effectively suppressed both Th1 and Th2 antibody responses, which was characterized by reduction in serum allergen-specific IgE, IgG, IgG1, and IgG2a levels as well as in interleukin-5 and interferon-γ levels in BALF and in OVA-incubated splenocytes. Meanwhile, regulatory cytokine, interleukin-10, was enhanced. Transplantation of iPSC-w/o-c-Myc also significantly attenuated cellular infiltration in BALF and allergic airway hyperresponsiveness. However, no tumor formation was observed 6 months after transplantation. Conclusions Administration of iPSC-w/o-c-Myc not only inhibited Th1 inflammatory responses but also had therapeutic effects on systemic allergic responses and airway hyperresponsiveness. iPSC-w/o-c-Myc transplantation may be a potential modality for treating allergic reactions and bronchial asthma.

Interferon-beta (IFN-β) treatment may not be effective in neuromyelitis optica (NMO). Whether the poor response to IFN-β is related to long spinal cord lesions (LSCL) or the NMO disease entity itself is unclear. We evaluated the spinal cord involvement of patients with multiple sclerosis (MS) and NMO, as well as the response after receiving IFN-β. Forty-nine MS and 21 NMO patients treated with IFN-β for at least 2 years from 2002-2008 were enrolled in this study and the treatment response was analyzed 2 years post-treatment. In the study, spinal cord lesions were present in 57.1% (28/49) of the MS patients, of which 16.3% (8/49) presented spinal cord lesions longer than 3 vertebral segments (LSCL). Responses to IFN-β treatment were seen in 69.3% (34/49) of all the MS cases, of which the appropriate response rates were 76.1% (16/21) in MS patients without spinal cord lesions and 37.5% (3/8) in patients with LSCL. Only 14.2% (3/21) of NMO patients responded to IFN-β treatment. In conclusion, spinal cord lesion is common in MS patients in Taiwan. Both NMO and MS patients with LSCL had a poor response to IFN-β treatment. NMO patients had a worse response to IFN-β treatment than MS patients with LSCL, which shows that the crucial structural defect is something other than LSCL such as the elevated serum IL17 level in NMO compared to MS.

Background This study investigated whether long-term treatment with antiepileptic drugs (AEDs) had negative effects on statural growth and serum calcium levels in children with epilepsy in Taiwan. Methods Children with epilepsy treated with one prescription of AEDs (monotherapy) for at least 1 year were selected. The AEDs included valproic acid (VPA; Deparkin) in 27 children (11 boys and 16 girls) aged 4-18 years, oxcarbazepine (Trileptal) in 30 children (15 boys and 15 girls) aged 5-18 years, topiramate (Topamax) in 19 children (10 boys and 9 girls) aged 6-18 years, and lamotrigine (Lamicta) in eight children (5 boys and 3 girls) aged 5-13 years. Patients with a history of febrile convulsions were selected as the controls. Results One year of VPA treatment significantly impaired the statural growth of pediatric patients with epilepsy (p Conclusions These results raise serious concerns about the growth of pediatric epilepsy patients who use AEDs, and potentially the need to closely monitor growth in children with epilepsy and adolescents under AED treatment, especially VPA.

Background Dravet syndrome (DS) is a rare form of intractable epilepsy. Children with DS often start having seizures in infancy, and gradually develop other seizure types. Several studies have demonstrated that certain gene mutations and submicroscopic copy number variations (CNV) in DS patients are strongly associated with intractable epilepsy. In this study, directed DNA sequencing and microarray technology were used to investigate genomic variations in DS patients. Methods A total of nine DS patients were enrolled in this genetic study. A detailed medical history was obtained from each participant, and appropriate neurological examinations performed. Seizure types and epilepsy syndromes were classified according to ILAE criteria. The complete coding regions of SCN1A, SCN1B, SCN2A, GABRG2, and GABRD, including the intron/exon boundaries, were sequenced using DNA samples drawn from participants. In addition, whole genome CNV analysis was conducted via SNP microarray analysis. Results DNA sequencing revealed a mutation in the SCN1A gene in five (55.6%) of the DS patients, within which three missense mutations, c.719T > C (p.Leu240Pro), c.2807A > T (p.Asp936Val), c.4349A > C (p.Gln1450Pro), and two frameshift mutations, c.2277insAACA (p.His759fsX772) and c.3972insT (p.Leu1324fsX1331) were observed. Upon CNV analysis, a novel duplication region, 4q13.1–q13.2, was detected in one DS patient; this variant region contained a gene, EPHA5, related to cerebral neuron development. Conclusion This study extended the spectrum of SCN1A mutations in Taiwanese DS patients and confirms the high sensitivity of SCN1A for the DS phenotype. In addition, a novel duplication region identified within EPHA5 should be considered in future screening procedures for DS.

The pre-ligand assembly domain (PLAD) of tumor necrosis factor receptors mediates specific ligand-independent receptor assembly and subsequent signaling. However, the physiological role of PLAD in the regulation of TNFR-mediated immune responses in autoimmunity is still unclear. By using the recombinant PLAD.Fc protein to block TNFR1 assembly, we demonstrated that PLAD.Fc treatment significantly reduced the TNFR1-driving proinflammatory cytokines and protected NOD mice from diabetes. Strikingly, Th17 differentiation was significantly inhibited in PLAD.Fc-treated NOD and TNFR1-deficient mice, indicating a TNFR1-dependent Th17 development. PLAD.Fc-modulated effects on DCs, in terms of the downregulation of Th17-inducing cytokines, IL-6 and TGF-β, explained the potential mechanism for Th17 suppression. Finally, we provided an additional result that PLAD.Fc administration diminished the infiltration of Th17 cells in the central nervous system and ameliorated the experimental autoimmune encephalomyelitis in mice. Collectively, these data demonstrated that targeting PLAD of TNFR1 provides protection from autoimmune diseases through the downregulation of Th17 and suggested a therapeutic potential of PLAD-modulation in TNF-involved inflammatory diseases.

Skin infection and/or nasal carriage of Staphylococcus aureus in children with atopic dermatitis (AD) is a risk factor for exacerbating disease or subsequent recurrent S. aureus infection. The purpose of the study is to evaluate the antibiotic susceptibilities of S. aureus strains from AD children and determine the most appropriate choice of antibiotics.Nasal swabs from 168 healthy children with AD and 20 AD children with concurrent skin and soft-tissue infections (SSTI) were collected in 2005-2008. S. aureus strains were further analyzed for and compared with antibiotic susceptibilities.There were 78 (46.4%) healthy children with AD colonized with S. aureus, and 24 (30.8%) were methicillin-resistant S. aureus (MRSA). Among the 20 SSTI-infecting strains, 12 (60%) were MRSA. Antimicrobial susceptibility testing showed that, after penicillin, colonizing and SSTI-infecting strains had the highest rates of resistance to erythromycin (50% and 70%, respectively). All isolated strains were susceptible to vancomycin, rifampin, and mupirocin. Multi-drug resistance was found in 70% of the colonizing and 50% of the SSTI-infecting strains. D-test assay revealed inducible clindamycin resistance in 75% of the colonizing strains. The most prevalent resistance gene was ermB which was present in 94.9% and 92.9% of colonizing and SSTI-infecting strains, respectively.This study found that colonizing and SSTI-infecting strains of S. aureus from AD children had a high prevalence of MRSA and multi-drug resistance. Trimethoprim-sulfamethoxazole, rifampin, fusidic acid and mupirocin appear to be more suitable for treatment and decolonization of S. aureus in AD children.

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, regulates immune responses through competing with receptors of Fas ligand (FasL), LIGHT and TNF-like molecule 1A (TL1A). We have previously demonstrated that transgenic expression of DcR3 in a β cell-specific manner significantly protects non-obese diabetic (NOD) mice from autoimmune diabetes. In this study, we further investigated the systemic effect of DcR3 in regulating lymphocytes and dendritic cells in NOD mice. Our results demonstrated that both DcR3 plasmid and protein treatments significantly inhibited insulitis and diabetes. Lymphocytes from DcR3.Fc-treated mice revealed less proliferative potential and transferred ameliorated diabetes. By administration of DcR3.Fc in T1 and T2 double transgenic NOD mice expressing human Thy1 or murine Thy1.1 surface marker under IFN-γ or IL-4 promoter control respectively, we observed a remarkable reduction of Th1 and an increase of Th2 immune responses in vivo. Strikingly, in vitro polarization experiments exhibited that not only Th1 but also Th17 cell differentiation was significantly inhibited in splenocytes treated with DcR3.Fc protein. However, this phenomenon was only observed in splenocytes, not in purified CD4(+) T cells, suggesting that DcR3-mediated inhibition of Th1 and Th17 differentiation is not T cell-autonomous and maybe through other cell types such as dendritic cells. Finally, our results demonstrated that DcR3 directly modulates the differentiation and maturation of dendritic cells and subsequently regulates the differentiation and effector function of T cells.

Hypernatremic dehydration amongst exclusively breastfed neonates due to inadequate breastfeeding or underfeeding is a potentially devastating condition. We investigated the epidemiological and clinic features of hypernatremic dehydration.We retrospectively reviewed the medical records of neonates that were less than 28 days of age, weighingor =2000 g with gestational age of 36 weeks born between January 2002 and December 2005, who had meet the criteria of hypernatremic dehydration, including (1) exclusively breastfed; (2) loss of weight 12% or more from birth weight; and (3) serum sodium concentration of at least 150 mmol/L at presentation, that had been subsequently admitted to our institution.Totally nine cases were found during this four-year period, an incidence of 2.3 per 1000 live births. Involved infants' age at presentation ranged from 3 days to 14 days (mean t Standard Deviation = 7 +/- [3.8]); five presented symptoms or signs within the first week of life. Study-involved infants featured a birth-weight loss ranging from 12% to 29% (mean +/- [SD] = 17.0 +/- [5.9]), and also hypernatremia (mean +/- [SD] = 153.5 +/- [3.2] mEq/L ). Sodium concentration of breast milk ranged from 15 mEq/L to 54 mEq/L (mean +/- [SD]= 36.0 +/- [14.32]). Subsequently, all were supplemented with breast milk or, alternatively, formula. None of the study-involved neonates suffered subsequent complications or a relapse of their condition.Neonatal hypernatremic dehydration due to inadequate breastfeeding or underfeeding would appear to be a rather common problem. In order to avoid serious morbidity and mortality, all breastfed infants should receive regular follow-up by health-care worker. Furthermore, we advocate that all mothers should be taught the skills of breastfeeding, and warning signs of breastfeeding failure and hypernatremia, accompanied with the monitoring of the weight of infants until growth commences, in order to reduce the likelihood of this condition arising, especially for first-time mothers.

The aim of this study was to investigate the effects of adjunctive lamotrigine (LTG) in refractory epilepsy in Taiwan, especially including patients who had undergone ineffective epileptic surgeries. Totally, 27 recruited children and adolescents with refractory epilepsy were treated with LTG add-on therapy, but 23 were enrolled statistically during 2 years period trial. Ten of the 23 patients (43.5%), including 5 undergoing epileptic surgeries, before had a50% reduction in seizure frequency. Surprisingly, LTG was found to have excellent response in six patients with Lennox-Gastaut Syndrome (LGS), 5 of whom had received anterior 2/3 callosotomy prior to the trial. Non-seizure related positive effects were presented in 3 patients, including greater alertness and attentiveness in 2 patients and improvement in mood in one patient. This open trial found that LTG was an effective add-on anti-epileptic drug (AED) in Taiwanese children and adolescents with refractory epilepsy and in cases with LGS even after ineffective callosotomy.

To investigate the kinetic changes in adaptive immunity during experimental Haemophilus influenzae type b (Hib) meningitis, we established a murine meningitis model based on T1/T2 doubly transgenic mice. These mice carry two transgenes that express two distinct cell-surface markers: a human Thy1 transgene (hThy1) under the control of the murine IFN-gamma promoter, and a murine Thy1.1 transgene (mThy1.1) under the control of the murine IL-4 promoter, designated T1 and T2, respectively. Mice infected with Hib displayed severest symptoms and lowest total splenocyte counts on day 3 after infection. Simultaneously, we examined the significantly low percentage of CD19+ B cells, the relatively high level of CD4+ T cells and significantly high percentage of CD8+ T cells in Hib-infected mice. Furthermore, we observed the early induction of both Th1 and Th2 responses, in terms of the augmentation of Th1 cells (IFN-gamma-producing CD4+ T cells) and Th2 cells (IL-4-producing CD4+ T cells) in Hib-infected mice. On day 7 after infection, the Th1 response gradually declined and the Th2 response rather sustained. Two weeks after infection, both Th1 and Th2 cells were barely detectable. Moreover, we demonstrated using an antigen-specific re-stimulation test to analyze the effector function of lymphocyte subsets that CD8+ T cells contributed to more predominantly production of IFN-gamma than CD4+ T cells did; and CD4+ T cells partly contributed to the secretion of IL-4 from flowcytometry of intracellular cytokine staining. Our results support that these transgenic mice provide an available model to dissect the complex kinetic change of adaptive immunity in bacterial infectious diseases.

Moyamoya disease is a neurological disease rarely seen in children outside Japan. It is difficult to differentiate moyamoya disease in its early stage from mitochondrial disorders in children when nontraumatic ischemic stroke is considered. We present a 14-month-old Taiwanese female child who had suffered from sudden onset of nontraumatic seizure attack, after which progressive left limb weakness was noted. Initial brain imaging and a series of laboratory studies were performed which suggested mitochondrial disorders, especially mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) syndrome. The patient underwent an oral glucose lactate stimulation test (OGLST), and mitochondrial disorders were not favored. MR angiography of the circle of Willis showed moyamoya disease. The patient then underwent an encephalo-duro-arterio-myo-synangiosis (EDAMS) operation. Evaluation of the neurodevelopmental and intelligence outcome required close long-term follow-up.

Background Staphylococcus aureus is an important cause of infection, particularly in persons colonized with this organism. This study compared the annual prevalence and microbiological characteristics of methicillin-resistant S. aureus (MRSA) nasal colonization in Taiwanese children from 2004 through 2009. Risk factors for MRSA were determined for the overall study period. Methods Children from birth to ≤14 years of age presenting for health maintenance visits or attending 1 of 57 kindergartens were recruited. Nasal swabs were obtained, and a questionnaire was administered. The prevalence and microbiological characteristics of MRSA colonization were also calculated for two 3-year periods: 2004–2006 and 2007–2009. Results Cultures of the anterior nares were positive for S. aureus in 824 (25.8%) of the 3,200 children, and MRSA colonization was found in 371 (11.6%) children. The prevalence of S. aureus colonization decreased from 28.1% in 2004–2006 to 23.3% in 2007–2009 (p

Background Vagus nerve stimulation (VNS), an alternative method to manage patients with medically intractable epilepsy, has shown favorable results in reducing seizure relapse and improvements in quality of life. In 1997, the U.S. Food and Drug Administration approved the use of this device as an adjunctive therapy for intractable seizure in adults and adolescents older than 12 years of age. Methods We present a preliminary study of pediatric patients, who suffered from medically intractable seizure and underwent VNS implantation after observation of the baseline seizure frequency. Classification of epileptic syndrome, seizure patterns, age of onset, seizure frequency reduction and adverse effects were recorded. Results Patients who underwent VNS implantation included four adolescents and four children. The follow-up duration ranged from 9–33 months. All the patients were responders after the beginning of the stimulation. Five of the eight patients responded to VNS with a seizure frequency reduction rate > 50%, and four of the eight patients experienced a ≥ 90% seizure reduction. No significant adverse effects were noted in all patients during the observation period. Conclusion The effective management of medically intractable seizure remains challenging to most clinical physicians. In addition to ketogenic diet and epilepsy surgery, VNS provides an alternative way to manage this issue. Our results suggest that VNS is well tolerated in pediatric patients, and is a favorable and safe method of treating intractable seizure in common clinical practice.

Background Hypoxic-ischemia (HI) and inflammation are the two major pathogenic mechanisms of brain injury in very preterm infants. The neurovascular unit is the major target of HI injury in the immature brain. Systemic inflammation may worsen HI by up-regulating neuroinflammation and disrupting the blood–brain barrier (BBB). Since neurons and oligodendrocytes, microvascular endothelial cells, and microglia may closely interact with each other, there may be a common signaling pathway leading to neuroinflammation and neurovascular damage after injury in the immature brain. TNF-α is a key pro-inflammatory cytokine that acts through the TNF receptor (TNFR), and c-Jun N-terminal kinases (JNK) are important stress-responsive kinases. Objective To determine if TNFR1-JNK signaling is a shared pathway underlying neuroinflammation and neurovascular injury after lipopolysaccharide (LPS)-sensitized HI in the immature brain. Methods Postpartum (P) day-5 mice received LPS or normal saline (NS) injection before HI. Immunohistochemistry, immunoblotting and TNFR1- and TNFR2-knockout mouse pups were used to determine neuroinflammation, BBB damage, TNF-α expression, JNK activation, and cell apoptosis. The cellular distribution of p-JNK, TNFR1/TNFR2 and cleaved caspase-3 were examined using immunofluorescent staining. Results The LPS + HI group had significantly greater up-regulation of activated microglia, TNF-α and TNFR1 expression, and increases of BBB disruption and cleaved caspase-3 levels at 24 hours post-insult, and showed more cortical and white matter injury on P17 than the control and NS + HI groups. Cleaved caspase-3 was highly expressed in microvascular endothelial cells, neurons, and oligodendroglial precursor cells. LPS-sensitized HI also induced JNK activation and up-regulation of TNFR1 but not TNFR2 expression in the microglia, endothelial cells, neurons, and oligodendrocyte progenitors, and most of the TNFR1-positive cells co-expressed p-JNK. Etanercept (a TNF-α inhibitor) and AS601245 (a JNK inhibitor) protected against LPS-sensitized HI brain injury. The TNFR1-knockout but not TNFR2-knockout pups had significant reduction in JNK activation, attenuation of microglial activation, BBB breakdown and cleaved caspase-3 expression, and showed markedly less cortical and white matter injury than the wild-type pups after LPS-sensitized HI. Conclusion TNFR1-JNK signaling is the shared pathway leading to neuroinflammation and neurovascular damage after LPS-sensitized HI in the immature brain. Electronic supplementary material The online version of this article (doi:10.1186/s12974-014-0215-2) contains supplementary material, which is available to authorized users.