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Abstract Background Child abuse in Taiwan is a major societal concern that severely affects the well-being of children. Despite the complexity in detecting abuse, reports of child abuse are increasing, evidenced by a rise in cases and heightened awareness. This study utilizes judicial judgments as a lens to understand the varied interpretations of child abuse by clinical and forensic experts and explores the broader epidemiological trends of such abuse within the declining youth population of Taiwan. Methods We conducted a retrospective study by analyzing official court judgments on child abuse allegations judged from 2008 to 2022 from the online database of Judicial Yuan. Furthermore, the study analyzed demographic factors, injury patterns, and opinions from various experts. Results The results reveal that severe criminal cases of child abuse predominantly involve biological fathers as the primary offenders and physical abuse as the most common form of maltreatment. Victims are typically aged less than 5 years, which frequently leads to an unfavorable prognosis. Analysis also highlights the TEN-4-FACESp acronym as a highly predictive indicator of child abuse and underscores the prevalence of abusive head trauma (AHT). Moreover, the findings emphasize ongoing disparities in opinions between forensic medical examiners and clinical physicians, especially in AHT cases, which potentially influences judicial decisions. Conclusions In summary, the study reveals ongoing disagreements between forensic medical examiners and clinical physicians, especially in cases of AHT, which may impact judicial decisions. Promoting consensus through interdisciplinary collaboration and improved communication can aid in revealing the truth in child abuse cases.

Background: Septic shock is the progression of sepsis, defined as cardiovascular dysfunction during systemic infection, and it has a mortality rate of 40 %–80 %. Loss of vascular tone is an important pathophysiological feature of septic shock. Diastolic blood pressure (DBP) was reported to be associated with vascular tone. This study aimed to identify the associations of several hemodynamic indices, especially DBP, with outcome in pediatric septic shock to allow for timely interventions. Methods: Children with persistent catecholamine-resistant shock had a pulse index continuous cardiac output (PiCCO®) system implanted for invasive hemodynamic monitoring and were enrolled in the current study. Serial cardiac index, systemic vascular resistance index (SVRI), systolic blood pressure (SBP), mean arterial pressure (MAP), and DBP were recorded during the first 24 h following PiCCO® initiation. All hemodynamic parameters associated with 28-day mortality were further analyzed using receiver operating characteristic curve analysis. Results: Thirty-three children with persistent catecholamine-resistant shock were enrolled. The median age was 12 years and the youngest children were 5 years old. Univariate analysis noted that SVRI, SBP, MAP, and DBP were significantly higher, and shock index was significant lower, in survivors compared with non-survivors (p 0.75, indicating a good prediction for mortality. Conclusions: DBP correlated well with SVRI and it can serve as a predictor for mortality in pediatric septic shock. Furthermore, DBP was a superior discriminator of mortality when compared with SBP and MAP. A lower DBP was an independent hemodynamic factor associated with 28-day mortality.

Background: The clinical presentations of abusive head trauma can abruptly worsen, so the occurrence of seizures and changes of EEG can be variable according to patients’ conditions. Since the changes of EEG background waves reflect the cortical function of children, we aimed to find out whether the timing of EEG background, epileptiform discharges and seizure patterns were associated with the outcomes of patients with AHT. Material and methods: Using seizure type and acute stage electroencephalographic (EEG) characteristics to assess adverse neurological outcomes in children with seizures secondary to abusive head trauma (AHT). Children who were hospitalized with AHT at a tertiary referral hospital from October 2000 to April 2010 were evaluated retrospectively. A total of 50 children below 6 years of age admitted due to AHT were included. KOSCHI outcome scale was used to evaluate the primary outcome and neurological impairment was used as secondary outcome after 6 months discharge. Results: Children with apnea, cardiac arrest, reverse blood flow and skull fracture in clinic had a higher mortality rate even in the no-seizure group (3/5 [60%] vs. 3/45 [6.7%], odds ratio [OR] = 11; 95% CI = 2.3–52; p = 0.025). Seizure occurrence reduced mostly at the second day after admission in seizure groups; but children with persistent seizures for 1 week showed poor neurological outcomes. The occurrence of initial seizure was frequency associated with younger age; focal seizure, diffuse cortical dysfunction in acute-stage EEG, and low Glasgow Coma Scale (GCS) score were significantly related to poor outcomes after 6 months. Diffuse cortical dysfunction was also associated with motor, speech, and cognitive dysfunction. Conclusions: Diffuse cortical dysfunction in acute-stage EEG combined with low GCS score and focal seizure may related to poor outcomes and neurological dysfunctions in children with AHT.

Abstract Objective Given the scarcity of studies analyzing the clinical predictors of pediatric septic cases that would progress to septic shock, this study aimed to determine strong predictors for pediatric emergency department (PED) patients with sepsis at risk for septic shock and mortality. Methods We conducted chart reviews of patients with ≥ 2 age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) criteria to recognize patients with an infectious disease in two tertiary PEDs between January 1, 2021, and April 30, 2022. The age range of included patients was 1 month to 18 years. The primary outcome was development of septic shock within 48 h of PED attendance. The secondary outcome was sepsis-related 28-day mortality. Initial important variables in the PED and hemodynamics with the highest and lowest values during the first 24 h of admission were also analyzed. Results Overall, 417 patients were admitted because of sepsis and met the eligibility criteria for the study. Forty-nine cases progressed to septic shock within 48 h after admission and 368 were discharged without progression. General demographics, laboratory data, and hemodynamics were analyzed by multivariate analysis. Only the minimum diastolic blood pressure/systolic blood pressure ratio (D/S ratio) during the first 24 h after admission remained as an independent predictor of progression to septic shock and 28-day mortality. The best cutoff values of the D/S ratio for predicting septic shock and 28-day mortality were 0.52 and 0.47, respectively. Conclusions The D/S ratio is a practical bedside scoring system in the PED and had good discriminative ability in predicting the progression of septic shock and in-hospital mortality in PED patients. Further validation is essential in other settings.

Abstract Background SARS-CoV-2 posed a threat to children during the early phase of Omicron wave because many patients presented with febrile seizures. The study aimed to investigate predicting factors for acute encephalopathy of children infected by SARS-CoV-2 Omicron variant presenting with febrile seizures. Methods The retrospective study analyzed data from pediatric patients who visited the emergency department of Chang Gung Memorial Hospital in Taiwan between April and July 2022. We specifically focused on children with COVID-19 who presented with febrile seizures, collecting demographic, clinical, and laboratory data at the pediatric emergency department, as well as final discharge diagnoses. Subsequently, we conducted a comparative analysis of the clinical and laboratory characteristics between patients diagnosed with acute encephalopathy and those with other causes of febrile seizures. Results Overall, 10,878 children were included, of which 260 patients presented with febrile seizures. Among them, 116 individuals tested positive for SARS-CoV-2 and of them, 14 subsequently developed acute encephalopathy (12%). Those with acute encephalopathy displayed distinctive features, including older age (5.1 vs. 2.6 years old), longer fever duration preceding the first seizure (1.6 vs. 0.9 days), cluster seizure (50% vs. 16.7%), status epilepticus (50% vs. 13.7%) and occurrences of bradycardia (26.8% vs. 0%) and hypotension (14.3% vs. 0%) in the encephalopathy group. Besides, the laboratory findings in the encephalopathy group are characterized by hyperglycemia (mean (95% CI) 146 mg/dL (95% CI 109–157) vs. 108 mg/dL (95% CI 103–114) and metabolic acidosis (mean (95% CI) pH 7.29(95% CI 7.22–7.36) vs. 7.39 (95%CI 7.37–7.41)). Conclusions In pediatric patients with COVID-19-related febrile seizures, the occurrence of seizures beyond the first day of fever, bradycardia, clustered seizures, status epilepticus, hyperglycemia, and metabolic acidosis should raise concerns about acute encephalitis/encephalopathy. However, the highest body temperature and the severity of leukocytosis or C-reactive protein levels were not associated with poor outcomes.

Background: A surge of encephalitis was reported in children during the early wave of the omicron epidemic in Taiwan. Information on the COVID-19-associated encephalitis, including epidemiologic features and factors of unfavorable outcomes, remained unclear. Methods: A total of 128 hospitalized Taiwanese children with laboratory-confirmed COVID-19 were enrolled between April 01, 2022, and May 31, 2022. The information on demographics and clinical features was abstracted from the medical records. Virologic lineages were determined by sequences of the spike protein. Factors associated with encephalitis and unfavorable outcomes were identified by comparisons to children without encephalitis and with favorable outcomes, respectively. Results: The leading syndromes associated with COVID-19 in hospitalized children were febrile seizure (20, 15.7%), fever as the solitary symptom (18, 14.1%), and croup syndrome (14, 10.9%). Encephalitis was diagnosed in nine (7.03%) children. When compared to the three leading syndromes, children with encephalitis were at older ages, had greater rates of hypotension, PICU admissions, use of inotropic agents (P

Children have been reported to be less affected and to have milder severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than adults during the coronavirus disease 2019 (COVID-19) pandemic. However, children, and particularly those with underlying disorders, are still likely to develop critical illnesses. In the case of SARS‐CoV‐2 infection, most previous studies have focused on adult patients. To aid in the knowledge of in-hospital care of children with COVID‐19, this study presents an expert review of the literature, including the management of respiratory distress or failure, extracorporeal membrane oxygenation (ECMO), multisystem inflammatory syndrome in children (MIS-C), hemodynamic and other organ support, pharmaceutical therapies (anti-viral drugs, anti-inflammatory or antithrombotic therapies) and management of cardiopulmonary arrest.

Background: Outbreak of Omicron BA.2 in Taiwan led to an increased number of acute encephalitis/encephalopathy cases in children and several fatal cases drew public attention. In pre-Omicron period, pediatric cases of COVID-19-associated acute encephalitis have been reported and during Omicron epidemic, febrile convulsions, encephalitis were mentioned more frequently. The outcome of patients with neurological complications was worse. However, few studies investigated the risk factors, pathophysiology and prognosis of COVID-19-associated encephalitis/encephalopathy. Here, we describe the presentation of pediatric cases of COVID-19-associated acute encephalitis/encephalopathy and explore the associated risk factors. Methods: Pediatric patients with confirmed SARS-CoV-2 infections were prospectively enrolled at admission at Chang Gung Memorial Hospital between April and August 2022. Patients were categorized into groups of acute encephalitis/encephalopathy, febrile convulsions or mild disease. Demographic descriptions, clinical manifestations and laboratory data were collected. Results: Of 288 acute COVID-19 patients, there were 38 (13.2%) acute encephalitis/encephalopathy, 40 (13.9%) febrile convulsions, and 210 (72.9%) mild disease. Among acute encephalitis/encephalopathy group, the mean age was 68.3 ± 45.0 months. The common neurological symptoms were lethargy (65.8%), seizures (52.6%), and impaired consciousness (34.2%). Over 3 years old (adjusted odds ratio [aOR]: 7.57, p

Background: Developmental dysplasia of the hip (DDH) is a common congenital disorder that may lead to hip dislocation and requires surgical intervention if left untreated. Ultrasonography is the preferred method for DDH screening; however, the lack of experienced operators impedes its application in universal neonatal screening. Methods: We developed a deep neural network tool to automatically register the five keypoints that mark important anatomical structures of the hip and provide a reference for measuring alpha and beta angles following Graf's guidelines, which is an ultrasound classification system for DDH in infants. Two-dimensional (2D) ultrasonography images were obtained from 986 neonates aged 0–6 months. A total of 2406 images from 921 patients were labeled with ground truth keypoints by senior orthopedists. Results: Our model demonstrated precise keypoint localization. The mean absolute error was approximately 1 mm, and the derived alpha angle measurement had a correlation coefficient of R = 0.89 between the model and ground truth. The model achieved an area under the receiver operating characteristic curve of 0.937 and 0.974 for classifying alpha

Abstract Objectives This study aimed to identify the predictors of neurologic outcomes and mortality in physically abused and unintentionally injured children admitted to intensive care units (ICUs). Methods All maltreated children were admitted to pediatric, neurosurgical, and trauma ICUs between 2001 and 2019. Clinical factors, including age, sex, season of admission, identifying settings, injury severity score, etiologies, length of stay in the ICU, neurologic outcomes, and mortality, were analyzed and compared between the physically abused and unintentionally injured groups. Neurologic assessments were conducted using the Pediatric Cerebral Performance Category scale. The study was approved by the Institutional Review Board of Chang Gung Memorial Hospital and the Ethics Committee waived the requirement for informed consent because of the anonymized nature of the data. Results A total of 2481 children were investigated; of them, there were 480 (19.3%) victims admitted to the ICUs, including 156 physically abused and 324 unintentionally injured. Age, history of prematurity, clinical outcomes, head injury, neurosurgical interventions, clinical manifestations, brain computed tomography findings, and laboratory findings significantly differed between them (all p

Abstract Purpose Our objective was to assess the adverse outcomes during pregnancy, as well as for the fetus and neonates, in women with epilepsy, both with and without the use of antiseizure medications (ASMs). Methods A cohort of singleton pregnancies between January 1, 2004 and December 31, 2014 was identified using the Taiwan National Health Database. The pregnancies were categorized into ASM exposure, ASM nonexposure, and control (consisting of women without an epilepsy diagnosis) groups. We recorded adverse outcomes in neonates and documented pregnancy complications. The generalized estimating equation with logit link was used to estimate adjusted odds ratios. Results There were 629 singleton pregnancies in the group exposed to ASMs, 771 in the epilepsy group without ASM exposure, and 2,004,479 in the control group. Women with epilepsy had a significantly higher risk of puerperal cerebrovascular diseases (adjusted odds ratios in the exposure and nonexposure groups = 54.46 and 20.37, respectively), respiratory distress syndrome (5.1 and 2.99), mortality (3.15 and 3.22), sepsis (2.67 and 2.54), pregnancy‐related hypertension (1.71 and 1.8), preeclampsia (1.87 and 1.79), cesarean delivery (1.72 and 2.15), and preterm labor (1.38 and 1.56). The use of ASMs may increase the risk of eclampsia (adjusted odds ratio = 12.27). Compared to controls, fetuses/neonates born to women with epilepsy had a higher risk of unexplained stillbirth (adjusted odds ratios in the exposure and nonexposure groups = 2.51 and 2.37, respectively), congenital anomaly (1.37 and 1.33), central nervous system malformation (3.57 and 2.25), low birth weight (1.90 and 1.97), and a low Apgar score at 5 min (2.63 and 1.3). The use of ASMs may introduce an additional risk of small for gestational age; the adjusted odds ratio was 1.51. Conclusion Women with epilepsy, irrespective of their exposure to ASMs, had a slightly elevated risk of pregnancy and perinatal complications. Puerperal cerebrovascular diseases may be a hidden risk for women with epilepsy.

Abstract Objective Bilateral frontoparietal polymicrogyria (BFPP) is a rare genetic‐related migration disorder. It has been attributed to loss‐of‐function of the ADGRG1 gene, which encodes an adhesion G protein‐coupled receptor, ADGRG1/GPR56. We report the EEG findings of BFPP in three Asian patients, and confirmed that change in protein function was caused by the novel missense variant (p.Leu290Pro). Methods We reviewed the medical records of three siblings with BFPP including one elder girl and two identical twin boys from birth to adulthood. The clinical symptoms, electroencephalography (EEG), brain MRI, whole‐exome sequencing, treatment including medications, neuromodulation, and epilepsy surgery, and clinical outcomes were reviewed. The protein structure of a novel missense variant (p.Leu290Pro) was predicted by in silico studies, and molecular analysis was performed via typical flow cytometry and Western blotting. Results The elder girl (Patient 1) was 22 years old and the twin boys (Patients 2 and 3) were 20 years old at the time of publication. All of them presented with typical clinical symptoms/signs and MRI findings of BFPP. Whole‐exome sequencing followed by Sanger confirmation showed that all three patients had compound heterozygous variants in the ADGRG1 gene. The missense variant (p.Leu290Pro) was confirmed to be related to a reduction in cell surface GPR56 expression. High‐amplitude rhythmic activity was noted in sleep EEG during infancy, which may have been due to excessive sleep spindle, and the rhythm disappeared when they were of pre‐school age. Partial callosotomy provided short‐term benefits in seizure control in Patients 1 and 2, and combined vagus nerve stimulation and partial callosotomy provided longer benefits in Patient 3. Significance Sleep EEG findings of high‐amplitude rhythmic activity in our BFPP cases were only noted during infancy and childhood. We also confirmed that the missense variant (p.Leu290Pro) led to loss of function due to a reduction in cell surface GPR56 expression.

IntroductionBronchopulmonary dysplasia (BPD) with pulmonary hypertension (PH) leads to increased morbidity and mortality in extremely preterm infants. Recent studies have analyzed factors associated with development of PH in BPD; however, this research remains inconclusive, and controversy exists regarding the correlation between BPD and PH. This study aimed to investigate potential associated factors, clinical characteristics, and outcomes of BPD with pulmonary hypertension in very low birth weight (VLBW) preterm infants.MethodsWe conducted a retrospective study, reviewing the records of infants with gestational age (GA)

Sepsis remains a major cause of morbidity and mortality among children worldwide. Furthermore, refractory septic shock and multiple organ dysfunction syndrome are the most critical groups which account for a high mortality rate in pediatric sepsis, and their clinical course often deteriorates rapidly. Resuscitation based on hemodynamics can provide objective values for identifying the severity of sepsis and monitoring the treatment response. Hemodynamics in sepsis can be divided into two groups: basic and advanced hemodynamic parameters. Previous therapeutic guidance of early-goal directed therapy (EGDT), which resuscitated based on the basic hemodynamics (central venous pressure and central venous oxygen saturation (ScvO2)) has lost its advantage compared with “usual care”. Optimization of advanced hemodynamics, such as cardiac output and systemic vascular resistance, has now been endorsed as better therapeutic guidance for sepsis. Despite this, there are still some important hemodynamics associated with prognosis. In this article, we summarize the common techniques for hemodynamic monitoring, list important hemodynamic parameters related to outcomes, and update evidence-based therapeutic recommendations for optimizing resuscitation in pediatric septic shock.

Anti-glutamic acid decarboxylase (anti-GAD) antibodies are associated with different types of syndromes. However, few studies have investigated the correlation between anti-GAD antibody titers with clinical severity and outcomes in children with encephalitis/encephalopathy. In this single-center retrospective cohort study, we consecutively enrolled hospitalized children who had encephalitis and/or encephalopathy with positive anti-GAD antibodies in serum and/or cerebrospinal fluid (CSF) from February 2010 to October 2021. Thirty-seven patients were included and divided into high-titer and low-titer groups. The patients with high anti-GAD antibody titers were associated with initial symptoms of language difficulty and ataxia. The level of titers was not associated with severity or outcomes. Anti-GAD antibody titers decreased after immunotherapy, however, the clinical response to immunotherapy was variable. A transient elevation in anti-GAD antibody titers during immunotherapy was noted. Further studies are warranted to investigate the role of anti-GAD antibodies in the pathogenesis and immune mechanisms of encephalitis/encephalopathy.

Background: Optic nerve sheath diameter (ONSD) ultrasound is a noninvasive and repeatable tool to dynamically evaluate intracranial pressure with high diagnostic accuracy; however, data in neonates are scarce. The aim of this study was to determine the reference value of ONSD and potential influencing factors in healthy term neonates. Methods: We retrospectively reviewed 250 full-term neonates who underwent cranial ultrasound as part of selective newborn screening over a 2-year period. Neonates with any of the following conditions were excluded: using mechanical ventilation, sedatives and/or vasopressors, or signs of infection which needed cerebrospinal fluid analysis and/or intracranial pathologies. Data on sex, gestational age, birth body weight, birth body height, birth head circumference, Apgar score and types of delivery were collected. The neurodevelopmental outcomes were reviewed. Results: A total of 234 neonates (123 girls and 111 boys) were included. The mean ONSD value was 3.30 ± 0.27 mm in the right eye and 3.30 ± 0.23 mm in the left eye, with no significant difference between both eyes (p = 0.797). Male neonates had a larger ONSD than female neonates (3.34 ± 0.22 mm versus 3.26 ± 0.20 mm, p = 0.007), and ONSD was correlated with birth weight in the males. Otherwise, there were no statistically significant associations between ONSD and other birth characteristics in both sexes. Most (63%) cases were followed for at least 12 months, and 98% had normal neurodevelopment. Conclusion: The reference value reported in this study may be used to evaluate the ONSD in healthy term neonates. Sex differences should be considered in this age group.

Background: Dravet syndrome is a severe developmental and epileptic encephalopathy characterized by the onset of prolonged febrile and afebrile seizures in infancy and SCN1A gene mutations. In some cases, non-SCN1A gene mutations can present with a phenotype very similar to that of Dravet syndrome. The aim of this study was to compare phenotypes of patients with SCN1A and non-SCN1A gene mutation-related Dravet syndrome. Methods: Thirty-six patients with Dravet syndrome-like phenotypes were followed from July 2017 to December 2019. We retrospectively analyzed their clinical profiles and genetic surveys. Results: Of the 36 enrolled patients, 15 (41.7%) had SCN1A mutations, one (2.8%) had an SCN8A mutation, one (2.8%) had an STX1B mutation, and five females (13.9%) had PCDH 19 mutations. The median age at first seizure onset was 7 months in those with SCN1A mutations, 1.3 years in those with PCDH19 mutations, and 10 months for the remaining patients. The majority of the patients with SCN1A mutations had status epilepticus (80% vs. 20%) and fever-sensitive seizures (76% vs. 31%) compared to those with PCDH19 mutations. The patients with SCN1A-related seizures had a higher rate of focal seizures as first seizure type than those without SCN1A mutations. Three of five (60%) patients with PCDH19 mutations had brain magnetic resonance imaging abnormalities. The three most commonly used antiseizure medications were sodium valproate, levetiracetam, and clobazam. Seven of the 15 patients with SCN1A mutations used stiripentol. The median time from seizure onset to genetic diagnosis was 6.6 years (range 4 months–22.3 years). Conclusion: The patients with SCN1A mutations in this study had high rates of fever-sensitive seizures, status epilepticus, seizure onset with focal seizure type, and relatively young age at seizure onset. The patients with PCDH19 mutations had a relatively high rate of abnormal brain magnetic resonance imaging findings.

In the pediatric intensive care unit (PICU), cardiac arrest (CA) is rare but results in high rates of morbidity and mortality. A retrospective chart review of 223 patients who suffered from in-PICU CA was analyzed from January 2017 to December 2020. Outcomes at discharge were evaluated using pediatric cerebral performance category (PCPC). Return of spontaneous circulation was attained by 167 (74.8%) patients. In total, only 58 (25%) patients survived to hospital discharge, and 49 (21.9%) of the cohort had good neurologic outcomes. Based on multivariate logistic regression analysis, vasoactive–inotropic drug usage before CA, previous PCPC scale >2, underlying hemato-oncologic disease, and total time of CPR were risk factors associated with poor outcomes. Furthermore, we determined the cutoff value of duration of CPR in predicting poor neurologic outcomes and in-hospital mortality in patients caused by in-PICU CA as 17 and 23.5 min respectively.

Background: Defective human TLR3 signaling causes recurrent and refractory herpes simplex encephalitis/encephalopathy. Children with febrile infection-related epilepsy syndrome with refractory seizures may have defective TLR responses. Methods: Children with febrile infection-related epilepsy syndrome were enrolled in this study to evaluate TLR1-9 responses (IL-6, IL-8, IL-12p40, INF-α, INF-γ, and TNF-α) in their peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (MDDCs), compared to those with febrile seizures and non-refractory epilepsy with/without underlying encephalitis/encephalopathy. Results: Adenovirus and enterovirus were found in throat cultures of enrolled patients (2–13 years) as well as serologic IgM elevation of mycoplasma pneumonia and herpes simplex virus, although neither detectable pathogens nor anti-neural autoantibodies in the CSF could be noted. Their PBMCs and MDDCs trended to have impaired TLR responses and significantly lower in cytokine profiles of TLR3, TLR4, TLR7/8, and TLR9 responses but not other TLRs despite normal TLR expressions and normal candidate genes for defective TLR3 signaling. They also had decreased naïve T and T regulatory cells, and weakened phagocytosis. Conclusion: Children with febrile infection-related epilepsy syndrome (FIRES) could have impaired TLR3, TLR4, TLR7/8, and TLR9 responses possibly relating to their weakened phagocytosis and decreased T regulatory cells.

Background: The aim of this study was to examine the predictive value of amplitude-integrated electroencephalography (aEEG) on 12-month seizure outcomes of infants with neonatal hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia. Methods: We conducted this retrospective cohort study in a tertiary neonatal intensive care unit between May 2012 and September 2017. Neonates with HIE who received both therapeutic hypothermia (TH) and aEEG were enrolled. Results: A total of 23 infants (14 boys, nine girls) with a mean gestational age of 38.9 weeks were enrolled. Fifteen (65%) infants had moderate HIE and eight (35%) had severe HIE according to modified Sarnat staging. The mean aEEG recording time was 107.5 h. Twenty (86.9%) infants had seizure activity during the first 24 h after cooling and 14 (60.8%) had seizure activity during the first 24 h after rewarming. At 12 months, five (21.7%) infants had poor seizure outcomes. Repetitive seizures or status epilepticus pattern during the first 24 h after rewarming, but not the first 24 h after cooling, were associated with the presence of epilepsy at 12 months (p = 0.037). Conclusions: We identified a high incidence of electrographic seizures in infants with neonatal HIE treated with therapeutic hypothermia, and post-neonatal epilepsy in the children who survived after HIE. Repetitive seizures or status epilepticus pattern during the first 24 h after rewarming, but not in the first 24 h after cooling, were associated with the presence of epilepsy at 12 months.

The rapid diagnosis of increased intracranial pressure is urgently needed for therapeutic reasons in neurocritically ill children, however this can rarely be achieved without invasive procedures. Point-of-care ultrasound of the optic nerve sheath diameter has been proposed as a non-invasive and reliable means to detect increased intracranial pressure in adults. Accordingly, clinicians may be able to use this technique to initiate early treatment and monitor the effectiveness of treatment in conjunction with other clinical examination and diagnostic modalities. Two meta-analyses and a systematic review have been published on this topic in adults. However, data on the correlation between optic nerve sheath diameter and intracranial pressure in neurocritically ill children are scarce. The aim of this review was to briefly describe what is being measured with point-of-care ultrasound of the optic nerve sheath diameter, summarize the most recent findings from adult literature, and provide an update of current work in children.

Acute encephalopathy is a life-threatening disease involving acute brain dysfunction, and it is one of the most important causes of mortality and severe neurological sequelae in infants and children. Approximately 30% of cases of acute encephalopathy result in some degree of neurological sequelae. Although many strategies have been proposed, effective therapies to ameliorate the outcomes of acute encephalopathy have not yet been established. Target temperature management (TTM), previously termed therapeutic hypothermia, has been shown to be effective for various brain injuries due to multiple neuroprotective mechanisms, and it may be considered to be the cornerstone of neuroprotective strategies. Consequently, TTM is currently used in the neurocritical care of adult patients with cardiac arrest with shockable rhythm and perinatal asphyxia. In addition, increasing evidence also indicates that TTM could be useful in other acute encephalopathies, including status epilepticus, acute encephalitis/encephalopathy and traumatic brain injury. In this review, we discuss the recent practical aspects of TTM as a potential intervention for various acute encephalopathies in children.

Background: To compare the clinical characteristics and outcomes of pediatric patients with refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) who received therapeutic hypothermia (TH) plus anticonvulsants or anticonvulsants alone. Methods: Two-medical referral centers, retrospective cohort study. Pediatric Intensive Care Unit (PICU) at Taoyuan Chang Gung Children's hospital and Kaohsiung Chang Gung Memorial Hospital. We reviewed the medical records of 23 patients with RSE/SRSE who were admitted to PICU from January 2014 to December 2017. Of these, 11 patients received TH (TH group) and 12 patients did not (control group). Results: The selective endpoints were RSE/SRSE duration, length of PICU stay, and Glasgow Outcome Scale (GOS) score. We applied TH using the Artic Sun® temperature management system (target temperature, 34–35 °C; duration, 48–72 h). Of the 11 patients who received TH, 7 had febrile infection-related epilepsy syndrome (FIRSE), one had Dravet syndrome, and three had traumatic brain injury. The TH group had significantly shortern seizure durations than did the control group (hrs; median (IQR) 24(40) vs. 96(90), p

Abstract Enterovirus A71 (EV-A71) is one of the causative pathogens of hand, foot, and mouth disease (HFMD), which may cause severe neurological and cardiopulmonary complications in children. In this review, we discuss the pathogenesis, clinical manifestations, management strategy, and clinical outcomes of cardiopulmonary failure (CPF) in patients with EV-A71 infection. The pathogenesis of CPF involves both catecholamine-related cardiotoxicity following brainstem encephalitis and vasodilatory shock due to cytokine storm. Sympathetic hyperactivity, including tachycardia and hypertension, are the early clinical manifestations of cardiopulmonary involvement, which may progress to pulmonary edema/hemorrhage and/or CPF. The management strategy comprises multidisciplinary supportive treatment, including fluid management, positive pressure ventilation support, and use of milrinone, vasopressors, and inotropes. Some patients may require extracorporeal membrane oxygenation. Major neurological sequelae are almost inevitable once a child develops life-threatening illness. Long-term care of these children is an important medico-social issue.

BackgroundTranscranial Doppler ultrasound is a sensitive, real time tool used for monitoring cerebral blood flow; it could provide additional information for cerebral perfusion in cerebral resuscitation during post cardiac arrest care. The aim of the current study was to evaluate the utility of a point-of-care transcranial Doppler ultrasound management algorithm on outcomes in pediatric asphyxial out-of-hospital cardiac arrest.MethodsThis retrospective cohort study was conducted in two tertiary pediatric intensive care units between January 2013 and June 2018. All children between 1 month and 18 years of age with asphyxial out-of-hospital cardiac arrest and a history of at least 3 min of chest compressions, who were treated with therapeutic hypothermia and survived for 12 h or more after the return of circulation were eligible for inclusion.ResultsTwenty-one patients met the eligibility criteria for the study. Sixteen (76.2%) of the 21 children were male, and the mean age was 2.8 ± 4.1 years. Seven (33.3%) of the children had underlying disorders. The overall 1-month survival rate was 52.4%. Twelve (57.1%) of the children received point-of-care transcranial Doppler ultrasound. The 1-month survival rate was significantly higher (p = 0.03) in the point-of-care transcranial Doppler ultrasound group (9/12, 75%) than in the non-point-of-care transcranial Doppler ultrasound group (2/9, 22.2%).ConclusionsPoint-of-care transcranial Doppler ultrasound group was associated with a significantly better 1-month survival rate compared with no point-of-care transcranial Doppler ultrasound group in pediatric asphyxial out-of-hospital cardiac arrest.

Aim: To identify the risk factors associated with the development of tracheobronchomalacia (TBM) in preterm infants with bronchopulmonary dysplasia (BPD).Methods: This was a retrospective cohort study using chart reviews of preterm infants born at ≤ 36 week's gestation who underwent flexible fiberoptic bronchoscopy in a tertiary pediatric referral center between January 2015 and January 2020. Indications for the bronchoscopy examination included lobar atelectasis on plain chest film, persistent CO2 retention, recurrent extubation failure, or abnormal breathing sounds such as wheeze or stridor. Optimal cutoff values for each risk factor were also determined.Results: Fifty-eight preterm infants with BPD were enrolled, of whom 29 (50%) had TBM. There were no significant differences in gestational age and birth weight between those with and without TBM. Significantly more of the patients with TBM had severe BPD compared to those without TBM (68.9 vs. 20.6%, p < 0.001). Clinical parameters that were significantly different between the two groups were included in multivariate analysis. Among these factors, severe BPD was the most powerful risk factor for the development of TBM (odds ratio 5.57, 95% confidence interval 1.32–23.5, p = 0.019). The areas under the receiver operating characteristic curves for peak inspiratory pressure (PIP) and the duration of intubation were 0.788 and 0.75, respectively. The best predictive cutoff values of PIP and duration of intubation for TBM were 18.5 mmHg and 82 days, respectively.Conclusion: Preterm infants with severe BPD are at high risk for the development of TBM, and the risk is even higher in those who receive a higher PIP or are intubated for longer. Bronchoscopy examinations should be considered for the early diagnosis and management of TBM in infants with these risk factors.

Background: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an anti-neuronal antibody-mediated inflammatory brain disease that causes severe psychiatric and neurological deficits in previously healthy patients. The aims of this study were to demonstrate the clinical characteristics of patients diagnosed with anti-NMDA receptor encephalitis and to compare the different treatment strategies among these patients. Methods: Patients presenting with newly acquired psychiatric and/or neurological deficits were studied retrospectively from 2009 to 2017. Patients with evidence of anti-NMDA receptor antibodies in serum and/or cerebrospinal fluid were enrolled. The modified Rankin scale was used to assess the initial status and outcomes of the enrolled patients. Details of the clinical presentations and results of investigations were analyzed. Results: All (n = 24) of the patients received first-line immunotherapy (steroids, and/or intravenous immunoglobulin, and/or plasma exchange), and 14 patients received second-line immunotherapy (rituximab and/or cyclophosphamide). The mean time between the first- and second-line treatment was 13 days. During the first 6 months, 20 patients (20/24, 83%) achieved a good outcome (modified Rankin Scale score ≤2) and 15 patients (15/24, 62.5%) completely recovered. Four patients (17.7%) relapsed, and three patients (12.5%) had associated tumors. Conclusion: Immunotherapy is an effective treatment for anti-NMDA receptor encephalitis. Rituximab and/or cyclophosphamide are treatment options for those who cannot tolerate or do not respond to first-line immunotherapy. Prospective studies are necessary to investigate the role of rituximab and cyclophosphamide in anti-NMDA receptor encephalitis. Key Words: cyclophosphamide, anti-NMDAR encephalitis, immunotherapy, intravenous immunoglobulin, rituximab

Abstract Background Myasthenia gravis is the most common disease affecting the neuromuscular junction. The most common etiology among patients with juvenile myasthenia gravis is the production of antibodies against the acetylcholine receptor. However, the clinical outcome in relation to serum levels of anti-acetylcholine receptor antibodies in juvenile myasthenia gravis has rarely been discussed. We aimed to analyze the correlation between the presence of anti-acetylcholine receptor antibodies and outcome in juvenile myasthenia gravis. Methods Patients diagnosed with juvenile myasthenia gravis younger than of 20 years of age were retrospectively recruited from January 1995 to February 2017 in a tertiary referral medical center. According to the Myasthenia Gravis Foundation of America outcome scale, the primary outcome was complete symptom remission and cessation of medications for at least 1 year measured 2 years after diagnosis. Secondary outcome was complete symptom remission at the last outpatient clinic. Results A total of 54 patients were followed up for over 2 years. Nine patients (9/54, 16.7%) achieved complete remission without medication use at 2 years after diagnosis. Thirteen (24.1%) patients achieved complete remission during longer follow-up periods. Those with negative anti-acetylcholine receptor antibodies were more likely to achieve complete remission at 2 years (6/15 [40%] vs. 3/39 [7.7%], 95% Confidence interval [CI] 1.670 to 38.323) and at the last outpatient clinic follow-up (8/15 [53.3%] vs. 5/39 [12.8%], 95% CI 2.367 to 20.704). Thirteen patients with comorbid autoimmune thyroid diseases were older than those without disease (11.8 ± 5.8 years old vs. 8.0 ± 6.3 years old, 95% CI 0.018 to 7.33). Moreover, patients negative for anti-acetylcholine receptor antibodies were less likely comorbid with autoimmune thyroid disease (1/35 [2.9%] vs. 12/71 [16.9%], 95% CI 0.018 to 1.161). Conclusions Juvenile myasthenia gravis patients without anti-acetylcholine antibodies exhibited significantly increased complete remission rates and a reduced likelihood of comorbid autoimmune thyroid diseases compared with those with anti-acetylcholine receptor antibodies among Chinese.

Abstract Background Pneumatosis intestinalis and portomesenteric venous gas are usually caused by necrotizing enterocolitis; however they can occur secondary to abusive abdominal trauma with bone fractures and bruising. It is difficult to recognize initially if there is no bruising on the skin or bone fractures. Case presentation We report a 1-year-old child with no obvious history of trauma who presented with conscious disturbance. Abdominal computed tomography showed acute ischemic bowel complicated with pneumatosis intestinalis and portomesenteric venous gas. The first impression was septic shock with acute ischemic bowel. Two weeks after admission, brain magnetic resonance imaging showed subdural hemorrhage of different stages over bilateral fronto-parietal convexities and diffuse axonal injury, suggesting abusive head trauma. He was subsequently diagnosed with occult child abuse. Conclusion Pneumatosis intestinalis and portomesenteric venous gas are rare except in cases of prematurity. Occult abusive abdominal trauma should be considered as a differential diagnosis in patients with pneumatosis intestinalis and portomesenteric venous gas, even without any trauma on the skin or bone fractures.

Aim: High-flow nasal cannulas (HFNCs) show potential in the application of positive pressure, improving gas exchange, and decreasing work of breathing in patients with acute respiratory distress. The aims of this study were to elucidate the indications for HFNC therapy in children of all ages and diagnoses, and to evaluate the efficacy and risk factors for failure of HFNC therapy in children with acute respiratory distress with hypoxia in a pediatric intensive care unit.Methods: We conducted this retrospective cohort study at a tertiary pediatric intensive care unit between January 1, 2018 and December 31, 2020. All children, from 1 month to 18 years of age, with acute respiratory distress with hypoxia and HFNC therapy were eligible. The clinical data were reviewed.Results: One hundred and two children met the eligibility criteria for the study, of whom 57 (55.9%) were male, and the mean age was 7.00 ± 6.79 years. Seventy-eight (76.5%) of the children had underlying disorders. The most common indications for the use of HFNC therapy were pneumonia (40, 39.2%), sepsis-related respiratory distress (17, 16.7%), and bronchiolitis (16, 15.7%). The failure rate was 15.7% (16 of 102 children). Higher initial and maximum fraction of inspiration O2 levels and lower initial and lowest SpO2/FiO2 (S/F) ratio were early and possible signs of failure requiring escalation of respiratory support.Conclusion: In our population, we found that HFNC therapy could be initiated as the first-line therapy for various etiologies of acute respiratory distress with hypoxia in a pediatric intensive care unit and for all age groups.

Background: Neonatal splenic rupture/hemorrhage (SRH), an extremely rare and potentially fatal presentation, can spontaneously resolve without surgical treatment; However, treatment approaches remain controversial. The present study aimed to describe and analyze the clinical features and therapies of neonatal SRH and therapeutic approaches.Methods: We present the cases of two patients and review another 37 cases reported in English-literature. The literature search included all articles published in PUBMED from inception between January 1968 and December 2019. Demographic data, precipitating factors, clinical characteristics including presenting symptoms and signs, presenting time, age at SRH presentation, imaging findings, as well as treatments and outcomes were analyzed.Results: In addition to the two cases treated at our hospital, 37 neonates with SRH were reported during the study period. The rate of full-term neonates was 72% (28/39). The cause was idiopathic in most cases, and congenital coagulation disorders were underlying causes in 13% (5/39) of the cases. The most common presenting symptom and sign of neonatal SRH were pallor or anemia, followed by abdominal discoloration/distension. Additionally, 18% (7/39) of the cases presented with scrotal hematoma or swelling. The age at SRH presentation ranged between 3 h and 5 days of age. Abdominal ultrasonography or computed tomography was used as the diagnostic tool. Twenty-seven cases (69%) received surgical management. The prognosis was comparable between the neonates treated with splenectomy and those treated with non-surgical approaches. The mortality rate was 18% (7/39) in the study cohort. SRH presentation at ≤12 h of age was associated with higher mortality compared to SRH presenting time at >12 h of age (odds ratio 25.0, 95% CI 2.514–248.575, p = 0.001).Conclusion: Our literature review revealed that the mortality rate of neonatal SRH was 18% and that the mortality risk was higher in neonates presenting with SRH symptoms and signs at ≤12 h of age.

Background: Neonatal encephalopathy is caused by a wide variety of acute brain insults in newborns and presents with a spectrum of neurologic dysfunction, such as consciousness disturbance, seizures, and coma. The increased excitability in the neonatal brain appears to be highly susceptible to seizures after a variety of insults, and seizures may be the first clinical sign of a serious neurologic disorder. Subtle seizures are common in the neonatal period, and abnormal clinical paroxysmal events may raise the suspicion of neonatal seizures. Continuous video electroencephalographic (EEG) monitoring is the gold standard for the diagnosis of neonatal seizures. The aim of this study was to identify the prevalence of electrographic seizures and the impact of monitoring in neonates with a high risk of encephalopathy. Methods: We conducted this prospective cohort study in a tertiary neonatal intensive care unit over a 4-year period. Neonates with a high risk of encephalopathy who were receiving continuous video EEG monitoring were eligible. The patients were divided into 2 groups: (1) acute neonatal encephalopathy (ANE) and (2) other high-risk encephalopathy conditions (OHRs). The neonates’ demographic characteristics, etiologies, EEG background feature, presence of electrographic seizures and the impact of monitoring were analyzed. Results: A total of 71 neonates with a high risk of encephalopathy who received continuous video EEG monitoring were enrolled. In this consecutive cohort, 42 (59.2%) were monitored for ANE and 29 (40.8%) were monitored for OHRs. At the time of starting EEG monitoring, 54 (76.1%) of the neonates were term infants. The median gestational age at monitoring was 39 weeks (interquartile range, 37–41 weeks). The median total EEG monitoring duration was 64.7 h (interquartile range, 22.2–72.4 h). Electrographic seizures were captured in 25 of the 71 (35.2%) neonates, of whom 20 (80%) had electrographic-only seizures without clinical correlation. Furthermore, of these 20 neonates, 13 (65%) developed electrographic status epilepticus. Electrographic seizures were most commonly found in the ANE group (17, 40.5%) than in the OHRs group (8, 27.6%) (p = 0.013). Besides, normal/mild abnormality and inactive EEG background were less electrographic seizure than moderate and major abnormality EEG background (2 of 30, 6.7% vs. 23 of 41, 56.1%, p < 0.001). Finally, continuous video EEG monitoring excluded the diagnosis of electrographic seizures in two-thirds of the monitored neonates who had paroxysmal events mimicking seizures and led to a change in clinical management in 39.4% of the neonates. Conclusions: Our findings showed that monitoring could accurately detect seizures, and that it could be used to guide seizure medication management. Therefore, continuous video EEG monitoring has important clinical management implications in neonates with a high risk of encephalopathy.

Background: The purpose of this study is to assess the roles of pediatric surgeons and adult trauma surgeons in the management of pediatric torso trauma patients in a Level I adult trauma center. Methods: From 2015 to 2019, pediatric torso trauma patients (age < 18 years) were studied. A comparison between patients who did and did not undergo surgery was performed. Older children (age: 10–18 years) were compared with young adults (age: 18–35 years) selected with the same criteria using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Results: A total of 226 patients were included in the study. Patients who underwent surgery for torso trauma (N = 61) were significantly older than patients who did not undergo surgery (N = 165) (13.1 vs. 10.4 years, p = 0.019). Both PSM and IPTW showed that the older children and young adult groups had similar proportions of patients requiring surgery (32.6% vs. 32.6%, standard difference (SD) = 0.000), proportions of patients who required torso angioembolization (8.7% vs. 9.8%, SD = 0.072), length of hospital stay (LOS) (8.1 vs. 8.0 days, SD = 0.026), and intensive care unit admission LOS (2.6 vs. 2.7 days, SD = 0.033). However, 7.1% of older children received critical care from pediatric surgeons. Additionally, 31.9% of younger children were cared for by pediatric surgeons/pediatricians. Conclusions: Adult trauma surgeons can feasibly perform surgeries for older children with torso trauma in collaboration with pediatric surgeons who provide critical care.

Aim: To analyze the factors associated with in-hospital mortality of children with acute fulminant myocarditis on venoarterial extracorporeal membrane oxygenation (VA-ECMO).Methods: This was a retrospective cohort study using chart reviews of patients diagnosed with acute fulminant myocarditis at the pediatric intensive care unit of two tertiary medical centers between January 1, 2005 and December 31, 2017. The inclusion criteria for this study were: (1) age from 1 month to 18 years; (2) diagnosed with acute myocarditis; (3) cardiogenic shock and need vasoactive-inotropic score ≥20 within 48 h after the use of vasoactive-inotropic agents; and (4) the need for ECMO placement.Results: Thirty-three children with acute fulminant myocarditis who needed ECMO were included. Clinical parameters were retrospectively reviewed. The overall survival rate was 69.6%. Higher levels of pre-ECMO troponin-I and pre-ECMO lactate, and lower post-ECMO left ventricular ejection fraction (LVEF) were significantly associated with in-hospital mortality in univariate analysis. Only higher pre-ECMO lactate and lower post-ECMO LVEF remained as predictors for in-hospital mortality in multivariate analysis. The areas under the curve of pre-ECMO lactate and post-ECMO LVEF in predicting survival were 0.848 (95% CI, 0.697–0.999, p = 0.002) and 0.824 (95% CI, 0.704–0.996, p = 0.01), respectively. A pre-ECMO lactate level of 79.8 mg/dL and post-ECMO LVEF of 39% were appropriate cutoff points to predict mortality.Conclusion: Pre-ECMO lactate level was associated with mortality in children with acute fulminant myocarditis, with an optimal cutoff value of 79.8 mg/dL. After VA-ECMO implantation, post-ECMO LVEF was associated with mortality, with an optimal cutoff value of 39%. The use of LVADs or urgent heart transplantation should be considered if the post-ECMO LVEF does not improve.

Objective: Valproic acid is the most high-risk teratogenic antiepileptic drug, and it may lead to fetal major congenital malformations. However, it is still used in women of childbearing age with epilepsy. The aim of this study was to report our experience of discontinuing or lowering valproic acid by adding levetiracetam, a low-risk teratogenic antiepileptic drug.Methods: We reviewed the medical records of childbearing age female patients with epilepsy who were treated with valproic acid initially and then switched to levetiracetam. The clinical profiles were recorded. The primary outcome was successful switching, which was defined as a decrease in the daily valproic acid dosage, after levetiracetam had been added.Results: Twenty-four female patients were enrolled (median age 22 years). The successful switching rate was 83.3% (20/24), and 55% (11/20) discontinued valproic acid after levetiracetam had been added. There were no significant differences between the successful and unsuccessful groups in etiology, electroencephalogram, and magnetic resonance imaging findings. Pharmacoresistant to levetiracetam was much higher in the unsuccessful group (45 vs. 100%). The median switching duration was 19.5 months in the successful group. There were improvements in metrorrhagia and alopecia in all of the patients in the successful group after valproic acid had been tapered.Conclusions: Our experience supports switching valproic acid to levetiracetam in childbearing age women with epilepsy as an effective strategy to lower the teratogenic rate and adverse effects. A long switching period was noted in this study. We suggest starting early in childbearing age women with epilepsy.

Traumatic brain injury (TBI) is a leading cause of pediatric morbidity and mortality and is categorized as abusive head trauma (AHT) and accidental head injury. A retrospective chart review of 124 children aged

Aim: The aim of the current study was to identify early clinical predictors of neurologic outcome in children with asphyxial out-of-hospital cardiac arrest (OHCA) treated with therapeutic hypothermia.Methods: The present retrospective cohort study of comatose children treated with therapeutic hypothermia or normothermia after asphyxial OHCA was conducted between January 2010 and June 2018. All children aged between 1 month and 18 years of age, with a history of at least 3 min of chest compressions were eligible for inclusion. Their 6-month neurological outcomes were evaluated using the Pediatric Cerebral Performance Category (PCPC) score and early clinical predictors were determined.Results: A total of 100 patients met the eligibility criteria for the study. Sixty-four (64%) of the children were male, and the mean age of participants was 4.59 ± 5.45 years. Forty (40%) of the children had underlying disorders. The overall 1-month survival rate was 36%. Only 12 (12%) of the patients had favorable outcomes (PCPC ≤ 2). Thirty-four (34%) of the 100 children were receiving therapeutic hypothermia. In the univariate analysis, an initial lactate level of ≤ 80 mg/dL, a Glasgow coma scale (GCS) score of 5–8, a GCS motor score ≥4 and a present pupil reflex before therapeutic hypothermia, were significantly associated with favorable 6-month neurological outcomes. However, after the multivariate logistic analysis, only initial serum lactate level and GCS before therapeutic hypothermia were significantly associated with favorable 6-month neurological outcomes.Conclusion: Initial serum lactate level and GCS before therapeutic hypothermia were significantly associated with 6-month favorable neurological outcomes in pediatric asphyxial OHCA patients who were treated with therapeutic hypothermia. Therefore, these early clinical predictors could be helpful to facilitate future clinical research in children with asphyxial OHCA treated with therapeutic hypothermia.

Background: In general clinical practice, neonatal seizures are identified visually by direct clinical observation. The study aimed to examine the frequency of clinical seizures in paroxysmal events in a neonatal intensive care unit. Methods: We conducted a prospective study of continuous video-EEG monitoring in a neonatal intensive care unit between January 2017 and December 2020. The demographic data were also reviewed. Results: Sixty-four neonates were enrolled. The median total video-EEG monitoring duration was 24.1 h (IQR 17.5–44.8 h). There were 309 clinically suspected seizure episodes, of which 181 (58.6%) were the motor type and 128 (41.4%) were the non-motor type. Only 63 (20.4%) of these events were confirmed to be clinical seizures on a simultaneous video-EEG recording. In terms of the impact of continuous video-EEG monitoring on clinical management, the anti-epileptic drugs were changed in 42 (65.6%) of the 64 neonates. Conclusion: In the identification of neonatal seizures, a clinical diagnosis by direct observation alone is not enough. The use of continuous video-EEG monitoring plays an important role in the diagnosis of neonatal seizures and in guiding clinical management decisions.

Background: Refractory septic shock can cause severe morbidities and mortalities in children. Resuscitation based on hemodynamics is important in children with critical illness. Thus, this study aimed to identify the hemodynamics of refractory septic shock associated with poor prognosis at an early stage to allow for timely interventions. Methods: We evaluated children with refractory septic shock admitted to a pediatric intensive care unit (PICU) and monitored their hemodynamics using a pulse index continuous cardiac output (PiCCO) system. The serial cardiac index (CI), systemic vascular resistance index (SVRI), and vasoactive–inotropic score (VIS) were recorded during the first 72 h after PICU admission. Results: Thirty-three children with refractory septic shock were enrolled. The SVRI and VIS were both associated with fatality from septic shock. The non-survivors had lower serial SVRI and higher VIS (both p < 0.05). Based on the area under the ROC curve, the SVRI was the predictor during the early resuscitative stage (first 36 h) in pediatric refractory septic shock. Conclusions: Both SVRI and VIS are predictors of mortality in children with refractory septic shock, and the SVRI is the powerful predictor of mortality in the early resuscitative stage. A low serial SVRI may allow for the early awareness of disease severity and strategies for adjusting vasoactive–inotropic agents to increase the SVRI.

Kawasaki disease (KD) is an acute systemic vasculitis of unknown cause that mainly affects infants and children and can result in coronary artery complications if left untreated. A small subset of KD patients with fever and cervical lymphadenitis has been reported as node-first-presenting KD (NFKD). This type of KD commonly affects the older pediatric population with a more intense inflammatory process. Considering its unusual initial presentation, a delay in diagnosis and treatment increases the risk of coronary artery complications. Herein, we report the case of a 9-year-old female with fever and neck mass that rapidly deteriorated to shock status. A diagnosis of KD was made after the signs and symptoms fulfilled the principal diagnostic criteria. The patient’s heart failure and blood pressure improved dramatically after a single dose of intravenous immunoglobulin. This case reminds us that NFKD could be the initial manifestation of KDSS, which is a potentially fatal condition. We review the literature to identify the overlapping characteristics of NFKD and KDSS, and to highlight the importance of early recognition of atypical KD regardless of age. We conclude that unusually high C-reactive protein, neutrophilia, and thrombocytopenia serve as supplemental laboratory indicators for early identification of KDSS in patients with NFKD.

Background: The neurologic outcomes of acute necrotizing encephalopathy (ANE) are very poor, with a mortality rate of up to 40% and fewer than 10% of patients surviving without neurologic deficits. Steroid and immunoglobulin treatments have been the most commonly used options for ANE, but their therapeutic efficacy is still controversial. Method: We retrospectively reviewed the medical records of 26 children diagnosed with ANE. We also divided these patients into two groups: 21 patients with brainstem involvement and 8 patients without brainstem involvement. Pulse steroid therapy (methylprednisolone at 30 mg/kg/day for 3 days) and intravenous immunoglobulin (2 g/kg for 2–5 days) were administered to treat ANE. Results: The overall mortality rate was 42.3%, and patients who did not survive had significantly higher initial lactate and serum ferritin levels, as well as higher rates of inotropic agent use with brainstem involvement. There were no significant differences in the outcomes of pulse steroid therapy or pulse steroid plus immunoglobulin between survivors and non-survivors. When analyzing the time between symptom onset and usage of pulse steroid therapy, pulse steroid therapy used within 24 h after the onset of ANE resulted in significantly better outcomes (p = 0.039). In patients with brainstem involvement, the outcome was not correlated with pulse steroid therapy, early pulse steroid therapy, or pulse steroid therapy combined with immunoglobulin. All patients without brainstem involvement received “early pulse methylprednisolone” therapy, and 87.5% (7/8) of these patients had a good neurologic outcome. Conclusion: Pulse steroid therapy (methylprednisolone at 30 mg/kg/day for 3 days) administered within 24 h after the onset of ANE may be correlated with a good prognosis. Further studies are needed to establish a consensus guideline for this fulminant disease.

Enterovirus 71 is a leading cause of hand-foot-and-mouth disease and herpangina. Here, the authors characterize a large panel of plasmablast-derived IgG mAbs that target the capsid of EV71 to identify neutralizing antibodies induced by natural infection.

Perinatal stroke is a common cause of established neurological sequelae. Although several risk factors have been identified, many questions regarding causes and clinical outcomes remain unanswered. This study investigated the clinical manifestations and outcomes of perinatal stroke and identified its etiologies in Taiwan. Methods: We searched the reports of head magnetic resonance imaging and computed tomography performed between January 2003 and December 2012. The medical records of enrolled infants with perinatal stroke were also reviewed. Results: Thirty infants with perinatal stroke were identified; 10 infants had perinatal arterial ischemic stroke (PAIS) and 20 had perinatal hemorrhagic stroke (PHS). Neonatal seizure was the most common manifestation and presented in 40% of infants with PAIS and 50% of infants with PHS. All survivors with PAIS and 77% of the surviving infants with PHS developed neurological sequelae. Acute seizure manifestation was associated with poststroke epilepsy in infants with PHS but not in infants with PAIS (86% vs. 0%, p=0.005). PAIS was mostly caused by dysfunctional hemostasis (20%) and embolism (20%), whereas PHS was mostly attributable to birth asphyxia (30%). Conclusion: Perinatal stroke is associated with high mortality and morbidity rates in infants. Clinically, it can be difficult to distinguish PAIS and PHS. One should keep a high level of suspicion, especially for PHS, if infants develop unexplained seizure, cyanosis, conscious change, anemia, and/or thrombocytopenia. A systematic diagnostic approach is helpful in identifying the etiologies of perinatal stroke.

Pediatric myocarditis symptoms can be mild or as extreme as sudden cardiac arrest. Early identification of the severity of illness and timely provision of critical care is helpful; however, the risk factors associated with mortality remain unclear and controversial. We undertook a retrospective review of the medical records of pediatric patients with myocarditis in a tertiary care referral hospital for over 12 years to identify the predictive factors of mortality. Demographics, presentation, laboratory test results, echocardiography findings, and treatment outcomes were obtained. Regression analyses revealed the clinical parameters for predicting mortality. During the 12-year period, 94 patients with myocarditis were included. Of these, 16 (17%) patients died, with 12 succumbing in the first 72 hours after admission. Fatal cases more commonly presented with arrhythmia, hypotension, acidosis, gastrointestinal symptoms, decreased left ventricular ejection fraction, and elevated isoenzyme of creatine kinase and troponin I levels than nonfatal cases. In multivariate analysis, troponin I > 45 ng/mL and left ventricular ejection fraction < 42% were significantly associated with mortality. Pediatric myocarditis had a high mortality rate, much of which was concentrated in the first 72 hours after hospitalization. Children with very high troponin levels or reduced ejection fraction in the first 24 hours were at higher risk of mortality, and targeting these individuals for more intensive therapies may be warranted.

Nonketotic hyperglycinemia (NKH) is a rare, inherited disease, with very poor outcome. It is difficult to confirm the diagnosis due to nonspecific presentations and rapid progression. The incidence was reported in a few countries. We report the clinical and genetic features of typical neonatal NKH with novel splicing mutation, c.1058+3A>C, in the intron 7 of the glycine decarboxylase (GLDC) gene. Furthermore, this study aimed to delineate the estimated incidence and clinical characteristics of NKH in the Taiwanese population. Methods: Reports of Health Promotion Administration, Ministry of Health and Welfare of Taiwan, during the period from 2000 to 2013; the Human Gene Mutation Database; and literature regarding NKH in Taiwan were reviewed. Demographic information, age of onset, clinical characteristics, genetic analysis, electroencephalography examinations, and outcome of the patients were analyzed. Results: The estimated incidence of NKH in the Taiwanese population was 7.2 cases per 1,000,000 live births. Among the 12 cases reported in Taiwan, more than 90% were of neonatal type. Fifty-five percent of affected patients died within 5 years, and all survivors had severe neurologic outcomes. Only three infants underwent genetic analysis during the study period. Two neonatal NKH infants had mutation in the GLDC gene, and the other one, who had late-onset NKH, had mutation in the glutaredoxin 5 gene. Conclusion: Compared with other countries, the estimated incidence of NKH was relatively rare in the Taiwanese population. It is important to characterize all index cases at the genetic level. With more awareness of NKH, increased knowledge of gene mutation, and improvement of diagnostic tools, NKH can be diagnosed more accurately.

Acute pediatric encephalitis with fulminant cerebral edema can rapidly become fatal or result in devastating neurological sequelae. Methods: All cases coded with the discharge diagnosis of acute encephalitis between January 2000 and December 2010 were reviewed. Of the 1038 children with acute pediatric encephalitis, 25 were enrolled in our study with ages ranging from 5 months to 16 years. Results: The major neurological symptoms included an altered level of consciousness (72%), vomiting (60%), and headache (48%). The onset of neurological symptoms to signs of brain herniation ranged from 0 days to 9 days. Nineteen (76%) patients had a seizure 24–48 hours prior to showing signs of fulminant cerebral edema, and 12 (48%) patients developed status epilepticus. Sixteen patients died, and no survivors returned to baseline. Risk factors for seizures and status epilepticus were compared between the fulminant cerebral edema group (n = 25, 19 seizures, including 12 status epilepticus) and control group (nonfulminant cerebral edema) (n = 1013, 444 seizures, including 141 status epilepticus; p = 0.001 for seizures and p

Serum lactate was used to predict the severity and outcome of neonatal hypoxic ischemic encephalopathy (HIE) before the era of therapeutic hypothermia (TH). There is no report on neurodevelopment (ND) outcome of neonates with HIE treated with TH in Taiwan. Methods: Between April 2011 and December 2012, newborn infants admitted to Chang Gung Memorial Hospital (CGMH), with gestational age > 35 weeks and birth weight ≥ 1800 g, who had acute perinatal events, evidence of significant fetal compromise, and ongoing clinical encephalopathy were prospectively enrolled for TH. Whole body cooling method was used to maintain the affected neonate's esophageal temperature at 33.5 ± 0.5°C for 72 hours. Demographic data were recorded and hemogram, biochemical parameters, serum lactate, and creatine kinase (CK) were measured as well. Brain magnetic resonance imaging (MRI) was performed between 7 and 14 days of life. ND outcome of infants was evaluated by Bayley Scales of Infant Development, third edition (BSID-III) at 24 months of corrected age. Poor ND (PND) outcome was defined as infants surviving with either disability or ND delay. Results: Seventeen patients were enrolled. Fifty-nine percent of babies (10/17) were born through cesarean section and 77% of babies (13/17) were transferred from outside hospitals. Six babies were moderate HIE and 11 babies were severe HIE. Among the 14 surviving patients, eight infants had PND outcome. There was no difference in demographic data between infants with and without PND. Serum level of lactate (mg/dL) after 72 hours of TH was higher (35.6 vs. 13.8, p = 0.042) in infants with PND. Neonates with abnormal brain MRI findings were also associated with PND (p = 0.01). Conclusion: This is the first report on ND outcome of neonates with HIE treated with TH in Taiwan. Higher serum level of lactate following TH and abnormal results of brain MRI are associated with poor ND outcome.

The recovery of diaphragmatic function is vital for successful extubation from mechanical ventilation. Recent studies have detected diaphragm atrophy in ventilated adults by using ultrasound, but no similar report has been conducted in children. In the current study, we hypothesized that mechanically ventilated children may also develop diaphragm atrophy and diaphragmatic dysfunction.Children who were admitted to the pediatric intensive care unit and were newly intubated for mechanical ventilation were enrolled into this prospective case-control study. Diaphragm ultrasound assessments were performed daily to evaluate diaphragmatic function in the enrolled children until their discharge from the pediatric intensive care unit. Diaphragm thickness and the diaphragmatic thickening fraction (DTF) were measured through these assessments.A total of 31 patients were enrolled, and overall, 1389 ultrasound assessments were performed. Immediately after intubation, the initial diaphragm thickness and DTF were measured to be 1.94 ± 0.44 mm and 25.85% ± 3.29%, respectively. In the first 24 hours of mechanical ventilation, diaphragm thickness and the DTF decreased substantially and decreased gradually thereafter. After extubation, the DTF was significantly different between the successful and failed extubation groups (P < 0.001), and a DTF value of

Endothelial dysfunction plays an important role in the pathophysiology of sepsis. As previously reported, the serum thrombomodulin is elevated in diseases associated with endothelial injury.The aim of this study was to investigate the association of serum thrombomodulin level in different pediatric sepsis syndromes and evaluate the relationship with disease severity and mortality.We prospectively collected cases of sepsis treated in a pediatric intensive care unit from June 2012 to July 2015 at Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and serum thrombomodulin levels were analyzed.Increased serum thrombomodulin levels on days 1 and 3 of the diagnosis of sepsis were found in different pediatric sepsis syndromes. Patients with septic shock had significantly increased serum thrombomodulin levels on days 1 and 3 [day 1: median, 6.9 mU/ml (interquartile range (IQR): 5.8-12.8) and day 3: median, 5.8 mU/ml (IQR: 4.6-10.8)] compared to healthy controls [median, 3.4 mU/ml (IQR: 2.3-4.2)] (p =