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The MELAS syndrome primarily affecting the CNS is mainly caused by the m.A3243G mutation. The heteroplasmy in different tissues affects the phenotypic spectrum, yet the impact of various levels of m.A3243G heteroplasmy on CNS remains elusive due to the lack of a proper neuronal model harboring m.A3243G mutation. We generated induced neurons (iNs) through the direct reprogramming of MELAS patients, with derived fibroblasts harboring high (>95%), intermediate (68%), and low (20%) m.A3243G mutation. iNs demonstrated neuronal morphology with neurite outgrowth, branching, and dendritic spines. The heteroplasmy and deficiency of respiratory chain complexes were retained in MELAS iNs. High heteroplasmy elicited the elevation in ROS levels and the disruption of mitochondrial membrane potential. Furthermore, high and intermediate heteroplasmy led to the impairment of mitochondrial bioenergetics and a change in mitochondrial dynamics toward the fission and fragmentation of mitochondria, with a reduction in mitochondrial networks. Moreover, iNs derived from aged individuals manifested with mitochondrial fission. These results help us in understanding the impact of various heteroplasmic levels on mitochondrial bioenergetics and mitochondrial dynamics in neurons as the underlying pathomechanism of neurological manifestations of MELAS syndrome. Furthermore, these findings provide targets for further pharmacological approaches of mitochondrial diseases and validate iNs as a reliable platform for studies in neuronal aspects of aging, neurodegenerative disorders, and mitochondrial diseases.

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

We have shown in vivo and in vitro previously that psychosine causes dysfunction of autophagy and the ubiquitin-proteasome system underlying the pathogenesis of globoid cell leukodystrophy (GLD), a devastating lysosomal storage disease complicated by global demyelination. Here, we investigated the therapeutic efficacy of the mTOR inhibitor rapamycin in twitcher mice, a murine model of infantile GLD, in biochemical, histochemical, and clinical aspects. Administration of rapamycin to twitcher mice inhibited mTOR signaling in the brains, and significantly reduced the accumulation of insoluble ubiquitinated protein and the formation of ubiquitin aggregates. The astrocytes and microglia reactivity were attenuated in that reactive astrocytes, ameboid microglia, and globoid cells were reduced in the brains of rapamycin-treated twitcher mice. Furthermore, rapamycin improved the cortical myelination, neurite density, and rescued the network complexity in the cortex of twitcher mice. The therapeutic action of rapamycin on the pathology of the twitcher mice’s brains prolonged the longevity of treated twitcher mice. Overall, these findings validate the therapeutic efficacy of rapamycin and highlight enhancing degradation of aggregates as a therapeutic strategy to modulate neuroinflammation, demyelination, and disease progression of GLD and other leukodystrophies associated with intracellular aggregates.

Primary intracranial ependymoma is a challenging tumor to treat despite the availability of multidisciplinary therapeutic modalities, including surgical resection, radiotherapy, and adjuvant chemotherapy. After the completion of initial treatment, when resistant tumor cells recur, salvage therapy needs to be carried out with a more precise strategy. Circulating tumor cells (CTCs) have specifically been detected and validated for patients with primary or recurrent diffused glioma. The CTC drug screening platform can be used to perform a mini-invasive liquid biopsy for potential drug selection. The validation of potential drugs in a patient-derived xenograft (PDX) mouse model based on the same patient can serve as a preclinical testing platform. Here, we present the application of a drug testing model in a six-year-old girl with primary ependymoma on the posterior fossa, type A (EPN-PFA). She suffered from tumor recurrence with intracranial and spinal seeding at 2 years after her first operation and extraneural metastases in the pleura, lung, mediastinum, and distant femoral bone at 4 years after initial treatment. The CTC screening platform results showed that everolimus and entrectinib could be used to decrease CTC viability. The therapeutic efficacy of these two therapeutic agents has also been validated in a PDX mouse model from the same patient, and the results showed that these two therapeutic agents significantly decreased tumor growth. After precise drug screening and the combination of focal radiation on the femoral bone with everolimus chemotherapy, the whole-body bone scan showed significant shrinkage of the metastatic tumor on the right femoral bone. This novel approach can combine liquid biopsy, CTC drug testing platforms, and PDX model validation to achieve precision medicine in rare and challenging tumors with extraneural metastases.

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.

The COVID-19 pandemic has evolved to immune escape and threatened small children and the elderly with a higher severity and fatality of non-pulmonary diseases. These life-threatening non-pulmonary COVID-19 diseases such as acute necrotizing encephalopathies (ANE) and multisystem inflammatory syndrome in children (MIS-C) are more prevalent in children. However, the mortality of multisystem inflammatory syndrome in adults (MIS-A) is much higher than that of MIS-C although the incidence of MIS-A is lower. Clarification of immunopathogenesis and genetic susceptibility of inflammatory non-pulmonary COVID-19 diseases would provide an appropriate guide for the crisis management and prevention of morbidity and fatality in the ongoing pandemic. This review article described three inflammatory non-pulmonary COVID-19 diseases including (1) meningoencephalitis (ME), (2) acute necrotizing encephalopathies (ANE), and (3) post-infectious multisystem inflammatory syndrome in children (MIS-C) and in adults (MIS-A). To prevent these life-threatening non-pulmonary COVID-19 diseases, hosts carrying susceptible genetic variants should receive prophylactic vaccines, avoid febrile respiratory tract infection, and institute immunomodulators and mitochondrial cocktails as early as possible.

Trapped temporal horn of lateral ventricle (TTHLV) is a rare condition of isolated focal hydrocephalus. We report two cases with different presentations, etiologies, and surgical managements. The first case involved an extremely preterm male baby with a history of ventriculitis and intraventricular hemorrhage; he received external ventricle drainage twice due to obstructive hydrocephalus. TTHLV was detected by sonography. He received a ventriculoperitoneal shunt involving two catheters to bypass the adhesion site. There was no ventricular dilatation during 2 years of follow-up. The second case involved a term baby with an enlarged head; brain sonography revealed left focal hydrocephalus with TTHLV and mild midline shift. Neuroendoscopic cystoventriculostomy with fenestration from the left trigone to the frontal horn was performed and serial follow-up brain sonography for 3 months showed decreased ventricle size. The suitable surgical techniques for the management of TTHLV should be adjusted according to the patients' condition to obtain more favorable outcomes. Brain sonography can be a useful tool for the diagnosis and for following up the surgical outcomes in infants with TTHLV.

Dravet syndrome (DS) is a rare and devastating epilepsy syndrome, and it can affect the patients and their caregivers. However, the lack of a reliable and valid measures of caregiver impact and the characteristic pattern in Taiwan. The purpose of this study was to describe the characteristics of patients with DS and caregivers’ concerns, and to establish a baseline frequency of characteristics of the disease using a cross-sectional survey in Taiwan. We recruit the caregivers of patients with DS and assessed their condition via online anonymous questionnaire. Seizure frequency decreased with age though not statistically significant. Vaccine may not influence the condition of DS. We highlighted the greatest impact on the domains that affect caregivers’ daily life, including additional household tasks, symptoms observation, further medical plan and financial problem. Caregivers may also concern about lack of independence/constant care, seizure control, speech/communication and sibling impacts/long-term care when patents are gone. The current findings highlight the significant life effects of caring for a child with DS in Taiwan, and can be used to raise the attention about the need for these families. The possible pathogenic mechanisms of these comorbidities were also discussed.

ObjectiveThe Yale Global Tic Severity Scale (YGTSS) is the most commonly used clinician-rated evaluation tool for Tourette syndrome (TS), with established reliability and validity. This study aims to determine whether the YGTSS is a valid parent-reported assessment in the TS population.DesignA prospective cohort study.SettingA major medical centre in Taiwan.MethodsA total of 594 patients were enrolled. A revised traditional Chinese version of the YGTSS was made available to parents via Google docs. Parents were encouraged to complete the YGTSS the day before each outpatient clinic visit. At each visit, a paediatric neurology fellow also administered the YGTSS assessment. We investigated whether differences in scores between physicians and parents changed as the number of parent evaluations increased. The results of the physician assessments were also taken as the expert standard for evaluating the sensitivity and specificity of the parent-reported assessments was conducted for the same visit.ResultsThe differences in the YGTSS scores between participants and physicians were small. The mean difference in the total assessment score was 4.15 points. As the number of times the parent evaluation was performed increased, the difference between the parent and physician scores decreased. Discrimination of moderate-to-severe attacks was good using the parent-assessed YGTSS (area under the receiver operating characteristic curve, 0.858; 95% CI 0.839 to 0.876). The sensitivity for detecting a moderate-to-severe attack by YGTSS parent assessment was 79.7% (95% CI 76.6 to 82.8), and the specificity was 91.8% (95% CI 89.9 to 93.7).ConclusionThe parent-reported YGTSS is a promising tool for TS assessment, demonstrating good discriminative ability for disease severity, with user precision increasing with experience.

Background To analyze the findings of cranial ultrasonographic screening in asymptomatic neonates and to assess the association between abnormal results and neurodevelopment. Methods We retrospectively reviewed the cranial ultrasonographic screening results of healthy neonates born between 35 and 42 weeks gestation at our hospital from October 2011 to October 2018. Results In total, 11,681 neonates underwent cranial ultrasonographic screening during the study period, and 9666 (82.7%) had normal results. Of 2015 neonates with abnormal findings, 294 had more than two abnormalities. The most common minor findings were subependymal cysts (8.99%), choroid plexus cysts (2.43%), lenticulostriate vasculopathy (2.34%), frontal horn cysts (1.80%), and enlarged cisterna magna (1.04%). Then, 33 (0.28%) neonates had major abnormalities, including cerebral hemorrhage, periventricular heterotopia, focal cortical dysplasia, anomalies of the corpus callosum, and vascular malformation. Of 1334 neonates who underwent serial clinical evaluations, 76 (5.69%) had neurodevelopmental disorders, including developmental delay, attention-deficit/hyperactivity disorder, and autistic spectrum disorder. Conclusion The incidence rate of intracranial anomalies in healthy neonates was 17.3%, and about 5.69% had neurodevelopmental disorders. Cranial ultrasonographic screening has its own value in helping early detection of intracranial anomalies in healthy neonates, some of which have prognostic implications.

Introduction Spinal muscular atrophy (SMA) is caused by a defect in the survival motor neuron 1 (SMN1) gene. The Cooperative Study of the natural history of SMA Type I in Taiwan is a retrospective, longitudinal, observational study that helps in further understanding SMA disease progression in patients who have not received disease-modifying therapeutic interventions. Methods Case report forms were used to collect demographics; genetic confirmation; SMN2 copy number; treatment patterns; and clinical outcomes including ventilator use, endotracheal tube intubation, tracheostomy, gastrostomy, complications, and survival. Results A total of 111 patients with SMA Type I were identified over the study period (1979–2015). Mean (median) age of onset and age at confirmed diagnosis were 1.3 (0.8) and 4.9 (4.4) months, respectively. SMN1 deletion/mutation was documented in 70 patients and SMN2 copy number in 32 (2 copies, n = 20; 3 copies, n = 12). At 240 months, survival probability for patients born during 1995–2015 versus 1979–1994 was significantly longer (p = 0.0057). Patients with 3 SMN2 copies showed substantially longer 240-month survival versus patients with 2 SMN2 copies. Over the 36-year period, mean (median) age at death was 31.9 (8.8) months. As of December 2015, 95 patients had died, 13 were alive, and 3 were lost to follow-up. The use of supportive measures (tracheostomy and gastrostomy) was associated with improved survival. Conclusions These data describe the short survival of patients with SMA Type I in Taiwan in the pretreatment era, emphasizing the positive impact of supportive measures on survival.

Background This study aimed to evaluate the demographic, clinical features, laboratory data, pathology and other survey in pediatric patients with cryofibrinogenemia. Methods A 12-year retrospective chart review identified eight pediatric patients at Mackay Memorial Hospital, Taipei, Taiwan. Results The female-to-male ratio was 3:1. The mean age at symptom onset and of diagnosis was 10.3 ± 4.6 years and 12.3 ± 4 years, respectively. One child (12.5%) had primary cryofibrinogenemia. The common symptoms were purpura, arthralgia, and muscle weakness (100%). On laboratory examination, cryofibrinogen was positive in all patients. All patients had increased anti-thrombin III while 87.5% and 62.5% had abnormal protein S and protein C, respectively. All eight also complained of neurologic symptoms. One had vertebral artery narrowing, two showed increased T2-weighted signal intensity on the thalamus or white matter, and one had acute hemorrhagic encephalomyelitis on brain magnetic resonance imaging. Conclusions This study reports on the presentations of cryofibrinogenemia, which is rare in children. Most cases are associated with autoimmune disease and have severe and complex presentations. Central nervous system involvement is common.

Neonatal brain tumor is rare and its outcome is generally poor. We reported a 17-day-old neonate presented as enlarged head girth. The pathological finding showed an embryonal tumor with multilayered rosettes.

Objectives The aim of this study was to establish reference ranges for the corpus callosum in infancy and to clarify how sexual dimorphism evolves between the fetal stage and infancy. Methods Normal sonograms from cerebral ultrasonographic examinations of 1- to 6-month-old healthy full-term infants were selected. The length and thickness of the corpus callosum were determined, and the effect of sex on these values was analyzed. Studies on corpus callosum sexual dimorphism were reviewed. Results In total, sonograms from 236 1- to 6-month-old infants (120 male and 116 female) were collected, and the typical values (5th-95th percentiles) of the corpus callosum were determined for each group. During the first 2 months, with and without brain size adjustment, the corpus callosum in female infants was significantly thicker than that in male infants (mean thickness ± SD: 1 month, male infant, 1.8 ± 0.3 mm; female infant, 2.1 ± 0.3 mm; P = .005; 2 months, male infant, 1.8 ± 0.2 mm; female infant, 2.0 ± 0.3 mm; P = .002). The corpus callosum thickness of male and female infants had no significant differences after 2 months of age. Sexual dimorphism was not detected in corpus callosum length. Conclusions Our study provides reference data on typical corpus callosum development in infants. In the fetal period and early infancy, the corpus callosum in female infants is thicker than that in male infants. From 3 months onward, the corpus callosum sexual dimorphism becomes insignificant throughout childhood. The evolvement of corpus callosum sexual dimorphism suggests that maternal factors may influence brain development.

// Dar-Shong Lin 1,2 , Shu-Huei Kao 3 , Che-Sheng Ho 1 , Yau-Huei Wei 2,10 , Pi-Lien Hung 4 , Mei-Hsin Hsu 4 , Tsu-Yen Wu 5 , Tuan-Jen Wang 6 , Yuan-Ren Jian 5 , Tsung-Han Lee 5 and Ming-Fu Chiang 7,8,9 1 Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan 2 Department of Medicine, Institute of Biomedical Sciences, Mackay Medical College, New Taipei, Taiwan 3 School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan 4 Department of Pediatric Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan 6 Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan 7 Department of Neurosurgery, Mackay Memorial Hospital, Taipei, Taiwan 8 Mackay Medicine, Nursing and Management College, Taipei, Taiwan 9 Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei, Taiwan 10 Center for Mitochondrial Medicine and Free Radical Research, Changhua Christian Hospital, Changhua, Taiwan Correspondence to: Dar-Shong Lin, email: // Ming-Fu Chiang, email: // Keywords : mitochondrial diseases, oxidative phosphorylation, bioenergetics, AMPK, metabolic inflexibility, Autophagy Received : June 08, 2017 Accepted : August 17, 2017 Published : September 01, 2017 Abstract Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is most commonly caused by the A3243G mutation of mitochondrial DNA. The capacity to utilize fatty acid or glucose as a fuel source and how such dynamic switches of metabolic fuel preferences and transcriptional modulation of adaptive mechanism in response to energy deficiency in MELAS syndrome have not been fully elucidated. The fibroblasts from patients with MELAS syndrome demonstrated a remarkable deficiency of electron transport chain complexes I and IV, an impaired cellular biogenesis under glucose deprivation, and a decreased ATP synthesis. In situ analysis of the bioenergetic properties of MELAS cells demonstrated an attenuated fatty acid oxidation that concomitantly occurred with impaired mitochondrial respiration, while energy production was mostly dependent on glycolysis . Furthermore, the transcriptional modulation was mediated by the AMP-activated protein kinase (AMPK) signaling pathway, which activated its downstream modulators leading to a subsequent increase in glycolytic flux through activation of pyruvate dehydrogenase. In contrast, the activities of carnitine palmitoyltransferase for fatty acid oxidation and acetyl-CoA carboxylase-1 for fatty acid synthesis were reduced and transcriptional regulation factors for biogenesis were not altered. These results provide novel information that MELAS cells lack the adaptive mechanism to switch fuel source from glucose to fatty acid, as glycolysis rates increase in response to energy deficiency. The aberrant secondary cellular responses to disrupted metabolic homeostasis mediated by AMPK signaling pathway may contribute to the development of the clinical phenotype.

Impairment of the ubiquitin-proteasome-system (UPS) and autophagy causing cytoplasmic aggregation of ubiquitin andp62 have been implicated in the pathogenesis of most neurodegenerative disorders, yet, they have not been fully elucidated in leukodystrophies. The relationship among impairment of UPS, autophagy, and globoid cell leukodystrophy (GLD), one of the most common demyelinating leukodystrophies, is clarified in this study. We examined the ubiquitin and autophagy markers in the brains of twitcher mice, a murine model of infantile GLD, and in human oligodendrocytes incubated with psychosine. Immunohistochemical examinations showed spatiotemporal accumulation of ubiquitin- and p62-aggregates mainly in the white matter of brain and spinal cord at disease progression. Western blot analysis demonstrated a significant accumulation of ubiquitin, p62, and LC3-II in insoluble fraction in parallel with progressive demyelination and neuroinflammation in twitcher brains. In vitro study validated a dose- and time-dependent cytotoxicity of psychosine upon autophagy and UPS machinery. Inhibition of autophagy and UPS exacerbated the accumulation of insoluble ubiquitin, p62, and LC3-II proteins mediated by psychosine cytotoxicity as well as increased cytoplasmic deposition of ubiquitin- and p62-aggregates, and accumulation of autophagosomes and autolysosomes. Further, the subsequent accumulation of reactive oxygen species and reduction of mitochondrial respiration led to cell death. Our studies validate the impairment of proteasome and autophagy underlying the pathogenesis of GLD. These findings provide a novel insight into pathogenesis of GLD and suggest a specific pathomechanism as an ideal target for therapeutic approaches.

To explore the effects of preferred music therapy on peer attachment, depression, and salivary cortisol among early adolescents.As adolescents enter puberty, they start to seek partnering relationships among peers. Peer attachment is central for adolescents and greatly influences their physical and psychological development.A pre-test-posttest control group design.The data were collected from July - October 2016. A total of 65 individuals were included. The treatment group received 40 min of music therapy twice per week over the course of 10 weeks. The control group maintained its typical routine. The research data were collected using structured questionnaires, including basic information, the Inventory of Peer Attachment, the Beck Depression Inventory-II questionnaires, and salivary cortisol concentrations. Statistical analysis methods included percentages, chi-square tests, t tests, analyses of covariance, and the Johnson-Neyman technique.There were statistically significant differences in peer attachment, depression, and salivary cortisol levels in the music group compared to the control group (p 0.05). Additionally, the findings showed that early adolescents with more severe depression experienced greater improvement through preferred music therapy.The results allude to the beneficial effects of receiving preferred music therapy in terms of the peer attachment, depression, and salivary cortisol levels of early adolescents. Adjustments should be made based on the characteristics of student groups to develop suitable and safe music therapy and to reduce the risks of poor mental health.目的: 探讨首选音乐疗法对早期青少年同伴依恋、抑郁和唾液皮质醇的影响。 背景: 随着青少年进入青春期,他们开始寻求同伴之间的伙伴关系。同伴依恋是青少年的中心,对他们的身心发展影响很大。 设计: 试验前-试验后控制组设计。 方法: 数据收集自2016年7月至10月。共有65人参加。治疗组在10周内每周接受两次40分钟的音乐治疗。对照组保持其典型的常规。研究数据采用结构化问卷收集,包括基本信息、同伴依恋量表、Beck抑郁量表II问卷和唾液皮质醇浓度。统计分析方法包括百分比、卡方检验、t检验、协方差分析和Johnson-Neyman技术。 结果: 音乐组的同伴依恋、抑郁和唾液皮质醇水平与对照组相比有统计学意义(P0.05)。此外,研究结果表明,抑郁更严重的早期青少年通过首选的音乐治疗经历了更大的改善。 结论: 研究结果表明,在早期青少年的同伴依恋、抑郁和唾液皮质醇水平方面,接受首选音乐治疗的会产生有益效果。应根据学生群体的特点进行调整,以发展合适、安全的音乐治疗,降低心理健康不良的风险。.

Background Corpus callosum atrophy has been associated with cognitive and motor deficits in elderly people. However, the role of the corpus callosum in infant development is unclear. The aim of this study was to assess the impact of corpus callosum size on motor development in infants. Methods We investigated cerebral ultrasonograms performed on healthy infants aged 4 to 6 months. The correlation between the development of rolling over and corpus callosum size was calculated for determining odds ratios. Covariates, including gestational age, sex, age in months, and head circumference were tested using logistic regression. Results We investigated 244 cerebral ultrasonograms performed on term infants from 2009 to 2011. The percentage of rolling over development in the examined infants increased with age (47.8%, 78.4%, and 97.5% at ages 4, 5, and 6 months, respectively). There was no significant difference in the development of rolling over between male (67.9%) and female (73.6%) children or among different gestational age groups. After the other covariates in the logistic model were adjusted, only age and corpus callosum size (length and thickness) were significantly associated with the development of rolling over: 3.86 times the odds (confidence interval, 2.1 to 7.0) for age in months, 1.14 times the odds (confidence interval, 1.0 to 1.3) for corpus callosum length, and 3.92 times the odds (confidence interval, 1.6 to 9.6) for corpus callosum thickness. Conclusions Corpus callosum size is positively associated with the development of rolling over in healthy term infants, independent of the gestational age, sex, age, and head circumference.

Aging is a complex biological process. A study of pyrroline-5-carboxylate reductase 1 (PYCR1) deficiency, which causes a progeroid syndrome, may not only shed light on its genetic contribution to autosomal recessive cutis laxa (ARCL) but also help elucidate the functional mechanisms associated with aging. In this study, we used RNA-Seq technology to examine gene expression changes in primary skin fibroblasts from healthy controls and patients with PYCR1 mutations. Approximately 22 and 32 candidate genes were found to be up- and downregulated, respectively, in fibroblasts from patients. Among the downregulated candidates in fibroblasts with PYCR1 mutations, a strong reduction in the expression of 17 genes (53.1%) which protein products are localized in the extracellular space was detected. These proteins included several important ECM components, periostin (POSTN), elastin (ELN), and decorin (DCN); genetic mutations in these proteins are associated with different phenotypes of aging, such as cutis laxa and joint and dermal manifestations. The differential expression of ten selected extracellular space genes was further validated using quantitative RT-PCR. Ingenuity Pathway Analysis revealed that some of the affected genes may be associated with cardiovascular system development and function, dermatological diseases and conditions, and cardiovascular disease. POSTN, one of the most downregulated gene candidates in affected individuals, is a matricellular protein with pivotal functions in heart valvulogenesis, skin wound healing, and brain development. Perturbation of PYCR1 expression revealed that it is positively correlated with the POSTN levels. Taken together, POSTN might be one of the key molecules that deserves further investigation for its role in this progeroid neurocutaneous syndrome.

The aim of this study was to establish reference ranges for the corpus callosum in infancy and to clarify how sexual dimorphism evolves between the fetal stage and infancy.Normal sonograms from cerebral ultrasonographic examinations of 1- to 6-month-old healthy full-term infants were selected. The length and thickness of the corpus callosum were determined, and the effect of sex on these values was analyzed. Studies on corpus callosum sexual dimorphism were reviewed.In total, sonograms from 236 1- to 6-month-old infants (120 male and 116 female) were collected, and the typical values (5th-95th percentiles) of the corpus callosum were determined for each group. During the first 2 months, with and without brain size adjustment, the corpus callosum in female infants was significantly thicker than that in male infants (mean thickness ± SD: 1 month, male infant, 1.8 ± 0.3 mm; female infant, 2.1 ± 0.3 mm; P = .005; 2 months, male infant, 1.8 ± 0.2 mm; female infant, 2.0 ± 0.3 mm; P = .002). The corpus callosum thickness of male and female infants had no significant differences after 2 months of age. Sexual dimorphism was not detected in corpus callosum length.Our study provides reference data on typical corpus callosum development in infants. In the fetal period and early infancy, the corpus callosum in female infants is thicker than that in male infants. From 3 months onward, the corpus callosum sexual dimorphism becomes insignificant throughout childhood. The evolvement of corpus callosum sexual dimorphism suggests that maternal factors may influence brain development.

Xq28 duplications encompassing the methyl CpG binding protein 2 (MECP2) in males exhibit a distinct phenotype, including developmental delay, facial dysmorphism, muscular hypotonia, intellectual disability, poor or absent speech, recurrent infections and early death. The vast majority of affected males inherit the MECP2 duplication from their usually asymptomatic carrier mothers. Only a few cases with Xq28 duplication originating from de novo unbalanced X/Y translocation have been reported and the paternal origin of the aberration has only been validated in three males in the related literature. Here we present a karyotypically normal male with features characteristic of the MECP2 duplication syndrome. The genome-wide SNP genotyping shows a de novo 2.26-Mb duplication from Xq28 to the terminus. The genotypes of the SNPs within the duplicated region indicated a paternal origin. Furthermore, the results of fluorescence in situ hybridization (FISH) indicated a novel Xq:Yp translocation, characterized as der(Y)t(Y;X)(p11.32;q28), which suggests an aberrant that occurred during spermatogenesis. The phenotype is compared to the previously reported cases with Xq28 duplication originated from an unbalanced X/Y translocation, and there was no specific part of the phenotype that could be contributed to the origin of parental imbalances. This report further highlights the capacity of high-molecular cytogenetic methods, such as SNP array and FISH, in the identification of submicroscopic rearrangement, structural configuration and parental origin of aberrant while in the evaluation of children with idiopathic developmental delay and intellectual disability.

Background The purpose of this study was to identify prognostic indicators of neurodevelopmental outcome in term infants who experienced clinical neonatal seizure. Methods This is a retrospective, observational hospital-based study. Term infants who experienced clinical neonatal seizure between January 1999 and December 2009 were enrolled. Adverse outcomes were defined as death, cerebral palsy, global developmental delay, and/or epilepsy. The associations between adverse outcomes and 17 variables, including sex, mode of delivery, being small of gestational age, maternal illness, perinatal insults, meconium stained liquor, Apgar score at 1 and 5 minutes, seizure onset age, seizure type, etiology, electroencephalography (EEG) findings, antiepileptic drug efficacy, presence of metabolic acidosis, and cranial ultrasonographic findings, and presence of congenital heart disease were analyzed. Results Among the 232 enrolled infants, 125 had a normal outcome and 14 had mild functional disability (59.9%), and 55 (23.7%) survived with one or more neurodevelopmental impairments (7 with cerebral palsy, 48 with global developmental delay), and 38 (16.4%) died. Forty-seven (23.0%) of the 204 patients who survived after the first discharge had epilepsy. Ten variables were associated with adverse outcome on univariate analysis, but only four variables, i.e., including abnormal cranial ultrasonography findings, abnormal anterior cerebral artery resistance index, abnormal EEG findings, and presence of congenital heart disease were independent predictors on multivariate logistic regression analysis. Conclusion In term infants with neonatal seizures, several risk factors related to adverse outcome were recognized. Physicians should pay more attention to these factors when handling patients with neonatal seizures.

Posterior fossa hemorrhage is rare in term baby and difficult to assess. The clinical signs are nonspecific and usually delay the diagnosis. We present a 5-day-old male neonate of posterior fossa hemorrhage with the initial presentations of fever and seizure and early deduced by cranial ultrasonography findings as hyperechoic, asymmetric, ill-defined density and complicated with hydrocephalus. Magnetic resonance imaging of the head verified the diagnosis. Hemophilia A was confirmed thereafter by serology.

We report a patient with congenital generalized lipodystrophy who had suffered from seizures, myoclonus, ataxia and cognitive decline since late childhood. Lafora disease was diagnosed based on skin biopsy results, which revealed pathognomonic Lafora bodies. The results of genetic analysis for mutations in EPM2A and EPM2B genes were negative. This is the first case report describing an association between congenital generalized lipodystrophy and Lafora disease. Further studies focusing on the relationship between these two diseases and the identification of a third locus for Lafora disease are needed.

Background Scrub typhus is a clinically important endemic disease in Taiwan. The aims of this study were to analyze the clinical manifestations, laboratory data and complications of pediatric scrub typhus in eastern Taiwan. Patients and Methods We searched medical records for all patients with scrub typhus who were hospitalized between 1992 and 2002 at the Taitung branch of Mackay Memorial Hospital, Taiwan. Records of children under the age of 18 with a confirmed diagnosis were selected for retrospective review. Results During the study period, 145 patients fulfilled the diagnostic criteria for scrub typhus, of whom 106 (73%) were adults and 39 (27%) were children. The mean age of the children was 7.6 ± 4.6 years. The most common clinical manifestations of pediatric scrub typhus were fever ( n = 39; 100%), cough ( n = 28; 72%), anorexia (72%), eschar (69%), chill (67%) and lymphadenopathy (64%). The most common complications were hepatic dysfunction (77%) and pneumonitis (54%). Three children (8%) required intensive care, but the overall survival rate was 97%. One child died with multi-organ failure within 8 hours after admission. Conclusion Scrub typhus should be considered in children with fever and hepatic dysfunction, particularly in those with a history of environmental exposure in an endemic area for scrub typhus. The presence of an eschar offers an important diagnostic clue, but not for all cases. Children with scrub typhus may develop serious complications and may even die if appropriate treatment is not given. Doxycycline is an effective antibiotic for pediatric scrub typhus in Taiwan.

Background: Prader–Willi syndrome (PWS) is a congenital disorder caused by absent expression of paternal genes in 15q11-13 affecting multiple systems. The information concerning the clinical features of this genetic disorder is incomplete in Taiwan. Methods: A retrospective analysis was carried out of 70 PWS patients (39 male, 31 females; age range, 1 month–22 years) seen in four major medical centers in Taiwan from January 1980 through June 2005. All cases were confirmed by methylation-specific polymerase chain reaction. The molecular characteristics, birth history, clinical presentation and laboratory studies were analyzed. Results: Complete genetic analysis was performed in 52 of the 70 patients with PWS. The abnormalities found included deletions in 45 (87%), maternal uniparental disomy (UPD) in five (10%), and a probable imprinting center deletion or an imprinting defect in two (4%). The average weight of the patients at birth was 2588 ± 540 g. Bone age delay of >2 years and growth hormone (GH) deficiency were noted in 11/40 (28%) and 12/20 (60%), respectively. In the 18 in whom both bone age and GH were assessed, abnormalities of both were found in two (11%). In 2000, Taiwan instituted the Rare Diseases and Orphan Drugs Act and mandated a three-phase screening protocol for PWS. Of the 41 patients diagnosed with PWS before 2000, only four (10%) were diagnosed before the age of 3 months; in the 29 patients diagnosed after 2000, in 15 (52%) the syndrome was confirmed before 3 months of age (P < 0.001). Conclusions: The present finding is in contrast to that of most previous reports that indicated a higher incidence of UPD in PWS. It is unclear whether this discrepancy in the incidence of UPD arises from under-diagnosis or because of ethnic differences, a question worthy of further study. The three-phase screening protocol has generated notable improvement in the early diagnosis of PWS in Taiwan.

Approximately 15% of preterm infants may develop postnatal cytomegalovirus (CMV) infection from seropositive mothers via breast milk and are at risk for neurological sequelae in childhood. The aims of this study were to assess the effects and outcomes on growth, neurodevelopmental status, and hearing in very low birth weight (VLBW) premature infants with postnatal CMV infection via breast milk at the corrected age of 12 and 24 months. The prospective follow-up study population comprised all living preterm children (n = 55) with a birth weight ≤1500 g and gestational age of ≤35 weeks, who had been participated in our “postnatal CMV infection via breast milk” studies in 2000 and 2009, respectively. The cohort of children was assessed at 12 and 24 months. Clinical outcomes were documented during hospitalization and after discharge. Long-term outcomes included anthropometry, audiologic tests, gross motor quotient, Infant International Battery, and neurodevelopmental outcomes; all were assessed at postcorrected age in 12 and 24 months during follow-up visits. Of the 55 infants enrolled in the study (4 noninfected infants were excluded because their parents did not join this follow-up program later), 14 infants postnatally acquired CMV infection through breast-feeding (infected group) and were compared with 41 infants without CMV infection (control group). No significant differences were observed between the groups with regard to baseline characteristics, clinical outcomes, anthropometry, or psychomotor and mental development on the Bayley scale of infant development. None of the infants had CMV-related death or permanent sensorineural hearing loss. Transmission of CMV from seropositive mother via breast milk to preterm infants does not appear at this time to have major adverse effects on clinical outcomes, growth, neurodevelopmental status, and hearing function at 12 and 24 months corrected age.

Globoid cell leukodystrophy (GLD) is an autosomal recessive, lysosomal storage disease caused by deficiency of the enzyme galactocerebrosidase (GALC). The absence of GALC activity leads to the accumulation of the toxic substance psychosine and the preferential loss of myelinating cells in the central and peripheral nervous systems. Profound demyelination, astrogliosis and axonopathy are the hallmarks of the pathogenesis of GLD, and cerebellar ataxia is one of the dominant manifestations in adolescents and adults affected with GLD. To date, studies regarding cerebellar degeneration in GLD are limited. In this study, the efficacy of cerebellum-targeted gene therapy on the cerebellar neuropathology in twitcher mice (a murine model of GLD) has been validated. We observed degeneration of Purkinje cells, Bergmann glia, and granule cells in addition to astrocytosis and demyelination in the cerebellum of the twitcher mice. Ultrastructural analysis revealed dark cell degeneration and disintegration of the cellular composition of Purkinje cells in untreated twitcher mice. In addition, the expressions of neurotrophic factors CNTF, GDNF and IGF-I were up-regulated and the expression of BDNF was down-regulated. Intracerebellar-mediated gene therapy efficiently corrected enzymatic deficiency by direct transduction to Purkinje cells and cross-correction in other cell types in the cerebellum, leading to the amelioration of both neuroinflammation and demyelination. The population, dendritic territory, and axonal processes of Purkinje cells remained normal in the cerebellum of treated twitcher mice, where radial fibers of Bergmann glia spanned the molecular layer and collateral branches ensheathed the dendritic processes of Purkinje cells. Moreover, the aberrant expressions of neurotrophic factors were mitigated in the cerebellum of treated twitcher mice, indicating the preservation of cellular function in addition to maintaining the neuronal architecture. The life span of the treated twitcher mice was significantly prolonged and their neurobehavioral performance was improved. Taken together, our findings underscore the complexity of cerebellar neurodegeneration in GLD and highlight the potential effectiveness of gene therapy in mitigating neuropathological deficits in GLD and other neurodegenerative disorders in which Purkinje cells are involved.

Objective: The initial clinical appearances of aseptic and bacterial meningitis in children are similar, but the treatment and outcome are quite different. To clarify the clinical presentation and laboratory results, we retrospectively reviewed our patients. Methods: The charts of hospitalized children under age 18 with discharge diagnosis of aseptic meningitis and bacterial meningitis during 2007~2014 were reviewed. Patients with aseptic meningitis were recruited as pleocytosis and negative bacterial growth in cerebrospinal fluid (CSF), while those with bacterial meningitis were recruited only who had positive CSF bacterial culture results. Traumatic tapping, contaminated cultures, or having received previous intravenous antibiotic therapy were excluded. Viral pathogens in CSF of aseptic meningitis were identified by CSF culture or polymerase chain reaction. Results: A total of 141 patients were enrolled as aseptic meningitis and 56 patients as bacterial meningitis. Aseptic meningitis occurred more in older than one-month-old children. Fever, headache, vomiting, and neck stiffness were significantly more in aseptic meningitis children, while convulsion, consciousness change, fontanelle bulging, and desaturation were significantly more in bacterial group. Significant laboratory differences were lymphocyte dominant in CSF, lower CSF protein level, higher CSF glucose level, and lower blood CRP level in aseptic meningitis group. Aseptic patients had shorter hospital duration (5.0 ± 2.0 days vs. 20.0 ± 8.0 days, p

Frontal horn cysts (FHCs) are elliptical, smooth, thin-walled cysts adjacent to the tip of the anterior horns of the lateral ventricles. Among 3,545 terms or near term healthy babies who underwent cranial ultrasound examination in our hospital over a 2-year 5-month period, 18 were found to have FHCs (17 typical and one atypical; seven bilateral and 11 unilateral, of which seven were on the left and four on the right). The female to male ratio was 2:1. The incidence of FHCs in normal term babies was thus 0.5%. Six children had resolution of the cyst within 1 month, and 6 more had resolution on repeat scan from 2 to 11 months of age. Four children did not have subsequent ultrasonography to document resolution, but they had normal growth and development. Two were lost to follow up. The infant with an atypical FHC had an enlarged left frontal horn cyst with a midline shift on follow up, but he had normal development. Our study suggests that FHC may be a normal physiologic variant or a benign pathologic condition that can be expected to resolve spontaneously within a few months. It is reasonable to follow typical FHC by cranial ultrasound examinations at 1 or 2 and 6 months of age. In the case of an atypical cyst, more frequent follow up and further image studies like CT or MRI are necessary.

Trisomy 18 is the second most common autosomal trisomy in newborns. The birth prevalence of this disorder is approximately 1 in 3,000 to 1 in 8,000, and the life span of the majority of patients is less than 1 year. As information regarding outcome in trisomy 18 is rather fragmentary in the literature, this study is aimed at investigating the survival and natural history of trisomy 18. We also evaluated the survival age and management of trisomy 18 in two different periods, before and after the implementation of National Health Insurance (NHI) program. Thirty-nine cases of trisomy 18 were collected in Mackay Memorial Hospital in a 17-year period, from 1988 to 2004. Delivery data, survival age, management before and after the implementation of NHI program, structural defects, image findings and cytogenetic results were analyzed by medical and nurse's records. The diagnosis of trisomy 18 was based on the prenatal amniocentesis or postnatal chromosome analysis. Three patients had trisomy 18 mosaicism. Since cardiovascular and central nervous systems are the most common organ systems involved in this disorder, 31 patients received brain ultrasonography and heart ultrasonography for evaluation of their multiple anomalies after admission. All patients except one died in their first year due to severe malformations of the cardiovascular or central nervous systems. The median survival age was 6 days. We found a longer survival with female patients than with male patients (P < 0.05). Implementation of NHI program in the more recent decade of this study period was associated with longer survival of trisomy 18 (P < 0.05). The three most common structural defects were clenched hands (95%), rocker bottom feet (90%), and low set or malformed ears (90%). Low birth weight was present in 90%. By cardiac ultrasonography, the top four heart defects were ventricular septal defect (94%), patent ductus arteriosus (77%) and atrial septal defect (68%). However, ten cases (32%) had complex congenital heart defects. By brain ultrasonography, the most common brain lesion was cerebellar hypoplasia (32%), followed by brain edema (29%), enlarged cisterna magna (26%) and choroid plexus cysts (19%). Although most patients with trisomy 18 die within the first few weeks after birth, it is important to recognize that a small but notable percentage of these patients will survive the first year. When prenatal or postnatal decisions need to be made, the possibility of long-term survival should be included in any discussion to enable families to make the most appropriate decision.

Isolated sulfite oxidase deficiency, a rare autosomal recessive inherited disorder, is easily misdiagnosed as the more common hypoxic-ischemic encephalopathy. A female term infant was diagnosed with isolated sulfite oxidase deficiency. Magnetic resonance imaging at ages 13 days, 2 months, and 10 months indicated diffuse edema with posterior predominance, followed by progressive multicystic encephalomalacia and brain atrophy with relatively sparing of the thalami. Single-photon emission computed tomography using 99m Tc-ethyl cysteinate dimer at 2 months revealed decreased uptake in the frontal lobes. The characteristic neuroimaging findings in isolated sulfite oxidase deficiency help differentiate it from hypoxic insult. The correct diagnosis is helpful in genetic counseling for parents.

Rationale: Septo-optic dysplasia (SOD) is a rare congenital disorder that may cause jaundice in infants. However, it is usually prone to neglect and misdiagnosis in infants with cholestasis because endocrine disorder such as panhypopituitarism is rare in the cause of infantile cholestasis. We report a case of SOD concurrent with acquired cytomegalovirus (CMV) infection, who presented with prolonged jaundice as the first clinical sign. Patient concerns: The patient was a 2-month-old male infant who presented with cholestasis, combined with fever and panhypopituitarism. Diagnoses: He was diagnosed with SOD and acquired CMV infection. Interventions: He was treated with hormone replacement therapy and ganciclovir. Outcomes: After correction of the pituitary hormone deficiency and ganciclovir treatment, significant improvements of cholestasis, retinal lesions, and growth rate were seen in our patient. Lessons: Although an endocrine disorder such as panhypopituitarism is rare in the cause of neonatal or infantile cholestasis, we must keep this reason in mind.

The authors report serial technetium-99m hexamethylpropylene-amine-oxime brain single photon emission computed tomography (SPECT) findings in two infants with Gaucher's disease type 2. Detailed neurologic and laboratory examinations, including bone marrow biopsies and enzymatic assays, were described. Serial brain magnetic resonance imaging studies in one patient illustrated the progressive cerebral atrophy in the frontal and temporal lobes. The SPECT in both cases demonstrated positive findings of initial scattered hypoperfusion, with extending to hypoperfusion of the entire cerebrum after 4 months of clinical deterioration. These changes in the SPECT findings may reflect progressive degeneration of the cerebrum in Gaucher's disease type 2. Brain SPECT may provide useful information on cerebral flow and metabolic distribution corresponding to the neurologic deficits of neuronopathic Gaucher's disease.

SCALP syndrome is an acronym describing the coincidence of sebaceous nevus syndrome, central nervous system malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus (giant congenital melanocytic nevus). We present a fourth case of this syndrome.

To report the successful use of rasburicase in two children with hyperuricemia secondary to severe rhabdomyolysis.: Case report.Pediatric intensive care unit in a freestanding quaternary hospital.Two pediatric patients with severe rhabdomyolysis and hyperuricemia caused by ecstasy intoxication and exertional heat stroke.Use of a single low dose (6 mg) of rasburicase, a urate oxidase enzyme.Rasburicase was administered on the first and second hospital days with a single low dose of 6 mg (0.086 mg/kg in patient A and 0.092 mg/kg in patient B). Within 24 hrs, the levels of serum uric acid in both patients decreased dramatically, and their creatinine levels decreased and urine output increased concurrently. Continuous improvements in the uric acid levels, creatinine levels, and urine output were noted during hospitalization.Rasburicase seems to be a safe and effective drug for improving hyperuricemia in patients with rhabdomyolysis and renal failure.

De Barsy syndrome (DBS) is characterized by progeroid features, ophthalmological abnormalities, intrauterine growth retardation, and cutis laxa. Recently, PYCR1 mutations were identified in cutis laxa with progeroid features. Herein, we report on a DBS patient born to a nonconsanguineous Chinese family. The exceptional observation of congenital glaucoma, aortic root dilatation, and idiopathic hypertrophic pyloric stenosis in this patient widened the range of symptoms that have been noted in DBS. Mutation analysis of PYCR1 revealed compound heterozygous PYCR1 mutations, including a p.P115fsX7 null mutation allele and a second allele with two missense mutations in cis: p.G248E and p.G297R. The effect of mutation results in a reduction of PYCR1 mRNA expression and PYCR1 protein expression in skin fibroblasts from the patient. The findings presented here suggest a mutation screening of PYCR1 and cardiovascular survey in patients with DBS. © 2011 Wiley Periodicals, Inc.

The autosomal recessive form of type II cutis laxa (ARCL II) is characterized by the appearance of redundant, inelastic skin with wrinkling, an aged look and additional variable systemic involvement including intrauterine growth retardation, failure to thrive, developmental delay, dysmorphism, osseous abnormality, and CNS manifestations. Several genetic defects have been found in patients and families with the clinical manifestations of ARCL II. Recently, mutations in PYCR1 have been linked to cutis laxa with progeroid features. We ascertained two siblings with of ARCL II born to non-consanguineous parents. Mutation analysis of PYCR1 revealed a novel single-base deletion (c.345delC) in exon 4 leading to frame-shift and premature stop of translation. The effect of this mutation results in a strong reduction of PYCR1 expression in skin fibroblasts from affected siblings. These two cases extend the genotypic spectrum of PYCR1-related ARCL II.

BACKGROUND: Carbon monoxide (CO) is an important source of poisoning in children. We performed this study in order to clarify the clinical characteristics of pediatric patients with CO poisoning. METHODS: We identified and reviewed the medical records of pediatric patients diagnosed with CO intoxication and hospitalized in our department during a 10-year period. Epidemiologic and clinical data were collected and analyzed. RESULTS: A total of 30 children with CO poisoning were identified. Their ages ranged from 2 to 17 years, with a mean of 9.5 +/- 4.5 years. Improperly vented exhaust produced by gas hot water heaters was the most common cause of intoxication (53.3%), followed by house fires (26.7%). Intentional poisoning by charcoal burning by parents occurred in six patients (20.0%). The majority of events occurred during cool seasons (76.7%). The most common presenting symptom was consciousness disturbance (86.7%). Only one child died and the mortality was 0.03%. Five (16.7%) children developed delayed neurologic sequelae (DNS), but they all recovered completely within 2 months. Seizures during the acute stage, severe metabolic acidosis, significant hypotension, longer times for recovery to full consciousness, and longer hospital stays were observed in children with DNS. CONCLUSION: Children with CO poisoning had good outcomes in this series. Although improperly vented exhaust from water heaters and house fires were the most common causes, intentional poisoning by parents through charcoal burning was also an important factor. Early identification of DNS risk factors might help to provide better care. Language: en

Facial palsy is an unusual complication associated with Kawasaki disease, with only a few published case reports. We report two patients with typical Kawasaki disease and facial palsy. Both had coronary artery aneurysms and were treated with intravenous immunoglobulin. The facial palsy resolved completely over the next several months in both patients. Coronary artery aneurysms resolved completely in one patient, and the other has not regressed to normal till now. The incidence of coronary artery aneurysm appears to be higher in the handful of reported cases of Kawasaki disease with facial palsy.

We report a newborn boy with the classic neonatal form of non-ketotic hyperglycinemia (NKH). He had a typical presentation of frequent hiccups and myoclonic movements since birth. Genetic analysis demonstrated a mutant allele with a single substitution at nucleotide 1111 of exon 8 (c. 1111 CG) in the GLDC gene inherited from his mother, resulting in a histidine-to-aspartic acid change at amino acid position 371 (p. His371Asp mutation) in the gene product. The other allele of the GLDC gene was deleted, a mutation inherited from the father.

This study investigated the survival and natural history of trisomy 13 in a series of patients, comparing the management and outcome before and after the implementation of Taiwan's National Health Insurance program (NHI).A total of 28 cases of trisomy 13 seen at Mackay Memorial Hospital, Taipei, Taiwan, from 1985 to 2004 were retrospectively reviewed. Survival and management before (12 cases) and after (16 cases) the implementation of National Health Insurance were compared, and structural defects, imaging findings, and cytogenetic results were analyzed. The cases that were diagnosed prenatally, and finally terminated, were excluded from this study. The diagnosis of trisomy 13 was based on the postnatal chromosome analysis.All patients except one with trisomy 13 translocation died in their first year because of severe malformations of the cardiovascular or central nervous system. The median survival was 9 days. After implementation of National Health Insurance, survival with trisomy 13 was significantly longer than before (P0.05). The three most common structural defects were abnormal auricular helices or low-set ears (89%), cryptorchidism and abnormal scrotum of male (73%) and cleft lip and/or palate (71%). Using echocardiography, the most commonly detected heart defects were patent ductus arteriosus (68%), ventricular septal defect (50%) and atrial septal defect (50%), and eight cases (36%) had complex congenital heart defects. The most common brain lesion was lenticulostriate vasculopathy (22%), followed by holoprosencephaly (17%), brain edema (13%) and subependymal cyst (13%).Early diagnosis and the survival patterns from the data collected should be used to inform parents and health-care professionals to assist in decision making. Although most patients with trisomy 13 die within the first weeks after birth, it is important to recognize that a few may survive the first year. When counseling families, the long-term survival prospects of trisomy 13 patients should be included.

Herpes simplex encephalitis (HSE) can cause high mortality and morbidity in children. Since local data of HSE in children are rare, we performed a retrospective study to evaluate the prognostic factors and outcome of HSE in Taiwan.Children were enrolled into this study if they were diagnosed as having encephalitis and also had positive polymerase chain reaction for herpes simplex virus (HSV) from cerebrospinal fluid, and/or positive immunoglobulin M or at least four-fold elevation of immunoglobulin G against HSV type 1 or type 2 from serum during the period from December 1, 1984 to January 31, 2003.Forty patients were enrolled in this study. Twenty six patients (65%) had good outcome and 14 (35%) had poor outcome. No mortality or recurrence was found. Three-fifths of the patients were between 1 year and 6 years of age. Fever (75%) was the most common finding at admission, followed by seizures (63%), lethargy (60%), and altered consciousness (48%). Seizure and lethargy at the time of admission were more common in the poor outcome group (71% vs 58% and 64% vs 58%). Abnormal computed tomography/magnetic resonance imaging findings were found in 63% of patients in whom the examinations were performed. Abnormal electroencephalogram (EEG) findings were noted in 79% of tested patients. Acyclovir was used to treat 29 patients (73%). Abnormal neuroimaging or EEG findings were more prevalent in patients with poor outcome (75% vs 55% and 92% vs 71%), as well as delayed (/=3 days) initiation of acyclovir therapy (92% vs 71%). There was no significant difference between the poor and good outcome groups in gender, age distribution, and clinical presentation.As we cannot predict the outcome of patients with HSE in the early beginning of illness and delay of treatment may cause disaster, early diagnosis and prompt acyclovir initiation are important requirements for successful management.

We performed a prospective study to evaluate the effect of topiramate as an adjunctive therapy in Taiwanese children with intractable partial epilepsy and generalized epilepsy. Thirty children aged from 2 to 16 years (8.5 +/- 3.8 years) were enrolled in this study. Eighteen children (60.0%) had partial epilepsy, and 12 children (40.0%) had generalized epilepsy. These children were experiencing more than one seizure per month even under a stable antiepileptic regimen treatment. Topiramate was begun at 1 mg/kg x day, and the dosage was raised by 1 mg/kg x day each week. Titration continued for 4 weeks or more. The maximal dosage was 10 mg/kg x day. In children with partial epilepsy, six children (33.3%) achievedor = 50% frequency reduction, while eight children (44.4%) achieved a seizure-free state. In children with generalized epilepsy, including infantile spasms, four children (33.3%) achievedor = 50% frequency reduction, while five children (41.7%) achieved a seizure-free state. The most common adverse effect was poor appetite (10.0%). No idiosyncratic reactions to topiramate were found. Only one patient discontinued topiramate because of central hyperventilation. Topiramate can be used as an adjunctive antiepileptic drug for intractable epileptic children in Taiwan.

Neurocutaneous melanosis (NCM) is a rare nonfamilial syndrome and characterized by large or numerous congenital melanocytic nevi and excessive proliferation of melanin-containing cells in the leptomeninges. It is believed to be an embryonic neuroectodermal dysplasia. Patients with NCM may develop severe hydrocephalus and other neurological symptoms with extremely poor prognosis. We report an infant with multiple large congenital melanocytic nevi and hydrocephalus. He was admitted to our hospital due to intermittent projectile vomiting and irritable crying for one week. CSF cytology and brain magnetic resonance imaging revealed central nervous system involvement. His condition was much improved after ventriculoperitoneal shunting. Even though patients with NCM and hydrocephalus may have normal growth and development after shunt insertion, close follow-up for these patients is still warranted.