Electroencephalogram pattern predicting neurological outcomes of children with seizures secondary to abusive head trauma.

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.

The impact of epilepsy and antiseizure medications on pregnancy and neonatal outcomes: A nationwide cohort study.

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.

Natalizumab Treatment for Relapsing Multiple Sclerosis Stabilises Normal-Appearing White Matter Microstructure: A One-Year Prospective Ultra-High-Field Quantitative Imaging Study.

(1) Background: Natalizumab dramatically reduces relapses and MRI inflammatory activity (new lesions and enhancing lesions) in multiple sclerosis (MS). Chemical exchange saturation transfer (CEST) MRI can explore brain tissue in vivo with high resolution and sensitivity. We investigated if natalizumab can prevent microstructural tissue damage progression measured with MRI at ultra-high field (7 Tesla) over the first year of treatment. (2) Methods: In this one-year prospective longitudinal study, patients with active relapsing-remitting MS were assessed clinically and scanned at ultra-high-field MRI at the time of their first natalizumab infusion, at 6 and 12 months, with quantitative imaging aimed to detect microstructural changes in the normal-appearing white matter (NAWM), including sequences sensitive to magnetisation transfer (MT) effects from amide proton transfer (MTRAPT) and the nuclear Overhauser effect (MTRNOE). (3) Results: 12 patients were recruited, and 10 patients completed the study. The difference in the T1 relaxation times at month 6 and month 12 of natalizumab treatment was not significant, suggesting the lack of accumulation of tissue damage, while improvements were seen in MTR (MTRAPT and MTRNOE measures) at month 12, suggesting a tissue repair effect. This paralleled the expected lack of clinical and radiological worsening of conventional MRI measures of disease activity (new lesions or gadolinium-enhancing lesions). (4) Conclusion: Natalizumab prevents microstructural brain damage and has effects suggesting an improved white matter microstructure measured at ultra-high field during the first year of treatment.

Natalizumab Treatment of Relapsing Remitting Multiple Sclerosis Has No Long-Term Effects on the Proportion of Circulating Regulatory T Cells.

INTRODUCTION: Natalizumab (NTZ), a monoclonal antibody against the integrin α4ß1 (VLA-4) found on activated T cells and B cells, blocks the interaction of this integrin with adhesion molecules of central nervous system (CNS) endothelial cells and lymphocyte migration through the blood-brain barrier, effectively preventing new lesion formation and relapses in multiple sclerosis (MS). Whether NTZ treatment has additional effects on the peripheral immune system cells, and how its actions compare with other MS disease-modifying treatments, have not been extensively investigated. In particular, its effect on the proportions of circulating regulatory T cells (Treg) is unclear. METHODS: In this study, we investigated the effect of NTZ treatment in 12 patients with relapsing MS, at 6 and 12 months after the start of treatment. We evaluated the proportions of regulatory T cells (Treg), defined by flow cytometry as CD4+ CD25++ FoxP3+ cells and CD4+ CD25++ CD127- cells at these intervals. As an exploratory study, we also investigated the NTZ effects on the proportions of bulk T and B lymphocyte populations, and of those expressing novel the markers CD195 (CCR5), CD196 (CCR6), or CD161 (KLRB1), which are involved in MS pathogenesis but have been studied less in the context of MS treatment. The effects of NTZ were compared to those obtained with 11 patients under interferon-beta-1a (IFN-ß1a) treatment, and against 9 healthy volunteers. RESULTS: We observed a transient increment in the proportion of Treg cells at 6 months, which was not sustained at 12 months. We observed a reduction in the proportion of T cells expressing CD195 (CCR5) and CD161 (KLRB1) subsets of T cells. CONCLUSION: We conclude that NTZ does not have an effect on the proportion of Treg cells over 1 year, but it may affect the expression of molecules important for some aspects MS pathogenesis, in a manner that is not shared with IFN-ß1a.

Sjogren's syndrome related autoimmune encephalopathy presenting as depression and involuntary agitation in a 15-year-old girl: a case report.

Introduction: Sjogren's syndrome is an autoimmune disease that commonly involves exocrinopathy. Although studies have reported psychiatric manifestations resulting from Sjogren's syndrome, few studies have focused on such manifestations in pediatric patients. Herein, we present a case of an adolescent girl with depression and involuntary self-harm behaviors related to Sjogren's syndrome with central nervous system involvement. Case presentation: A 15-year-old girl, with an underlying history of epilepsy, developed depressive symptoms of a year's duration, accompanied by three seizure episodes and involuntary self-harm behaviors. The self-harm behaviors, which included head banging and arm scratching, were sudden onset, involuntary, and unable to be recalled afterwards. After admission to our ward, the patient was positive for serum antinuclear antibodies and Schirmer's test. Moreover, 24-hour electroencephalography revealed epileptiform discharges during the mood swing episodes. Positive findings for antinuclear antibodies and anti-SSA antibodies in both serum and cerebrospinal fluid, suggested central nervous system involvement in Sjogren's syndrome. After rituximab treatment, her mood became euthymic, and her involuntary self-harm behaviors ceased. Conclusion: Central nervous system involvement leading to psychiatric presentations has rarely been reported in adolescents with Sjogren's syndrome. When treating adolescent patients with involuntary self-harm behaviors and neurological symptoms, it is crucial to consider autoimmune encephalitis related to Sjogren's syndrome in the differential diagnosis.

Long-Term Outcome of Neonatal Seizure with PACS2 Mutation: Case Series and Literature Review.

Phosphofurin Acidic Cluster Sorting Protein 2 (PACS2)-related early infantile developmental and epileptic encephalopathy (EIDEE) is a rare neurodevelopmental disorder. EIDEE is characterized by seizures that begin during the first three months of life and are accompanied by developmental impairment over time. In this article, we present three patients with EIDEE who experienced neonatal-onset seizures that developed into intractable seizures during infancy. Whole exome sequencing revealed a de novo heterozygous missense variant in all three patients in the p.Glu209Lys variant of the PACS2 gene. We conducted a literature review and found 29 cases to characterize the seizure patterns, neuroimaging features, the usage of anticonvulsants, and the clinical neurodevelopmental outcomes of PACS2-related EIDEE. The seizures were characterized by brief, recurring tonic seizures in the upper limbs, sometimes accompanied by autonomic features. Neuroimaging abnormalities were observed in the posterior fossa region, including mega cisterna magna, cerebellar dysplasia, and vermian hypoplasia. The long-term prognosis ranges from low-average intelligence to severe developmental retardation, emphasizing the importance of early recognition and accurate diagnosis by pediatric neurologists to provide personalized patient management.

Comorbidities of systemic lupus erythematosus prior to and following diagnosis in different age-at-onset groups.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a female-dominated autoimmune disease that can occur at any age and has a diverse course. The clinical manifestation of this disease can vary depending on the patient's age at onset. The aim of this study was to characterise the comorbidities at the time of SLE diagnosis and after in different age groups. METHODS: A total 1042 incident cases of SLE with a Catastrophic Illness Card in 2005 and 10,420 age- and sex-matched controls from the general population registered in the National Health Insurance Research Database in Taiwan were enrolled in the study. The risk of comorbidities before (adjusted odds ratio, [aOR]) and after (adjusted hazard ratio, [aHR]) of SLE was analysed. The burden of these SLE-associated comorbidities was weight by the Charlson comorbidity index (CCI). We used the cumulative incidence to evaluate the impact of comorbidities on different age onset groups. RESULTS: In this study, musculoskeletal diseases had the highest positive association (aOR, 5.29; 95% confidence interval [CI]: 4.25-6.57) prior to the diagnosis of SLE and they were also the most common developing incident comorbidity after the diagnosis (HR, 13.7; 95% CI: 11.91-15.77). It only took less than 1 year for 50% of the late-onset SLE patients to develop any increase in CCI score. The developing comorbidities attributed to 16.3% all-cause mortality and they had the greatest impact on late-onset SLE patients, with 33.3% cumulative incidence to all-cause mortality. There is no difference in the incidence of infectious diseases across different age groups. The herpes zoster infection had the greatest cumulative incidence among the category of infection diseases in child-onset SLE patients. CONCLUSION: SLE patients had increased risks of multiple pre-existing comorbidities at diagnosis. The developed comorbidity after diagnosis could contribute to all-cause mortality. The herpes zoster infection is primarily an issue in child-onset SLE patients.

Incidence and prevalence of Tourette syndrome and chronic tic disorders in Taiwan: a nationwide population-based study.

PURPOSE: The incidence of Tourette syndrome and chronic tic disorders has seldom been evaluated in Asia. METHODS: Using the National Taiwan Insurance Research Database, the annual standardized incidence and prevalence of Tourette syndrome (TS) and chronic tic disorders were estimated from 2007 to 2015. The pre-existing comorbidity at disease diagnosis was also evaluated. RESULTS: From 2007 to 2015, the age- and sex-standardized incidence increased from 5.34 (95% confidence interval [CI] 5.06-5.62) per 100,000 person-years to 6.87 (95% CI 6.53-7.21) per 100,000 person-years. In children and adolescents, the age- and sex-standardized incidence increased from 19.58 (95% CI 18.42-20.75) per 100,000 person-years to 31.79 (95% CI 30.09-33.49) per 100,000 person-years. In adults, the age- and sex-standardized incidence decreased from 2.01 (95% CI 1.79-2.23) per 100,000 person-years to 1.24 (95% CI 1.07-1.42) per 100,000 person-years. The incidence rate ratio (IRR) between males and females was 3.74 (95% CI 3.32-4.22). The age- and sex-standardized prevalence increased from 37.51 (95% CI 36.75-38.27) per 100,000 people in 2007 to 84.18 (95% CI 83.02-85.35) per 100,000 people in 2015. The rate risk (RR) between males and females was 3.65 (95% CI 3.53-3.78). CONCLUSION: The annual incidence rates of TS and chronic tic disorders increased in childhood and adolescence but decreased in adulthood from 2007 to 2015. The prevalence rates increased over the same period.

The clinical relevance of anti-glutamic acid decarboxylase antibodies in children with encephalitis/encephalopathy.

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.

Secular Trends in the Incidence, Prevalence, and Medications for Epilepsy from 2007 to 2015 in Taiwan: A Nationwide Population-Based Study.

BACKGROUND: Patients with epilepsy have a higher mortality rate than the general population. Up-to-date estimates of epilepsy incidence, prevalence, and medication use are critical to assist policymaking. METHODS: Using the National Taiwan Insurance Research Database, the standardized incidence and prevalence of epilepsy were estimated in each calendar year from 2007 to 2015. We used the incident cases of epilepsy to analyze the change in prescribing patterns from 2007 to 2015. Joinpoint regression was used to estimate secular trends. RESULTS: From 2007 to 2015, the age- and sex-standardized incidence decreased from 0.72 (95% confidence interval [CI] 0.70-0.73) to 0.54 (95% CI 0.53-0.55) per 1,000 person-years, giving an annual percentage change (APC) of -2.73 (p < 0.05). Among patients younger than 20 years, the incidence did not change significantly. The age- and sex-standardized prevalence decreased from 6.94 (95% CI 6.90-6.98) to 6.86 (95% CI, 6.82-6.89) per 1,000 people, giving an APC of -0.31 (p < 0.05). However, the prevalence increased in the 35- to 49- and 50- to 64-year age-groups. The most common first-line anticonvulsant was phenytoin in 2007 and valproate in 2015. The use of levetiracetam, clobazam, and valproate increased during the study period, with APCs of 25.48% (95% CI 19.97-31.24), 6.41 (3.09-9.85), and 2.83 (1.51-4.16), respectively. The use of carbamazepine, phenytoin, and topiramate decreased; the APCs were -23.86% (95% CI -25.25 to -22.44), -6.61 (-8.40 to -4.79), and -4.29% (-7.87 to -0.57), respectively. CONCLUSIONS: The overall prevalence and incidence of epilepsy decreased slightly from 2007 to 2015. The prescribed first-line anticonvulsant also changed over time.

Clinical spectrum and the comorbidities of Dravet syndrome in Taiwan and the possible molecular mechanisms.

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.

Genetics and clinical correlation of Dravet syndrome and its mimics - experience of a tertiary center in Taiwan.

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.

Low acuity paediatric emergency visits under single-payer universal health insurance in Taiwan, 2000-2015: a population-based repeated cross-sectional design.

OBJECTIVES: Emergency services utilisation is a critical policy concern. The paediatric population is the main user of emergency department (ED) services, and the main contributor to low acuity (LA) ED visits. We aimed to describe the trends of ED and LA ED visits under a comprehensive, universal health insurance programme in Taiwan, and to explore factors associating with potentially unnecessary ED utilisation. DESIGN AND SETTING: We used a population-based, repeated cross-sectional design to analyse the full year of 2000, 2005, 2010 and 2015 National Health Insurance claims data individually for individuals aged 18 years and under. PARTICIPANTS: We identified 5 538 197, 4 818 213, 4 401 677 and 3 841 174 children in 2000, 2005, 2010 and 2015, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: We adopted a diagnosis grouping system and severity classification system to define LA paediatric ED (PED) visits. Generalised estimating equation was applied to identify factors associated with LA PED visits. RESULTS: The annual LA PED visits per 100 paediatric population decreased from 10.32 in 2000 to 9.04 in 2015 (12.40%). Infectious ears, nose and throat, dental and mouth diseases persistently ranked as the top reasons for LA visits (55.31% in 2000 vs 33.94% in 2015). Physical trauma-related LA PED visits increased most rapidly between 2000 and 2015 (0.91-2.56 visits per 100 population). The dose-response patterns were observed between the likelihood of incurring LA PED visit and either child's age (OR 1.06-1.35 as age groups increase, p<0.0001) or family socioeconomic status (OR 1.02-1.21 as family income levels decrease, p<0.05). CONCLUSION: Despite a comprehensive coverage of emergency care and low cost-sharing obligations under a single-payer universal health insurance programme in Taiwan, no significant increase in PED utilisation for LA conditions was observed between 2000 and 2015. Taiwan's experience may serve as an important reference for countries considering healthcare system reforms.

Middle cerebral artery velocity is associated with the severity of MRI brain injury in neonates received therapeutic hypothermia.

BACKGROUND: No previous study has investigated the relationship between middle cerebral artery (MCA) flow velocity and the severity of hypoxic ischemic encephalopathy (HIE) evaluated by magnetic resonance imaging (MRI). The aim of this study was to assess the correlation between cerebral blood flow as assessed by transcranial Doppler sonography and the severity of MRI brain injury in asphyxiated neonates with clinical HIE who received therapeutic hypothermia. METHODS: This retrospective cohort study was conducted in the neonatal intensive care unit at Chang Gung Memorial Hospital between April 2011 and May 2014. All neonates with HIE who received therapeutic hypothermia, transcranial Doppler examinations, and brain MRI were eligible. Brain MRI was performed at 11 days of age (interquartile range: 8.5-15 days) and the severity of MRI brain injuries was evaluated using the MR scoring system proposed by Barkovich et al. Serial transcranial Doppler examinations were performed in pre-hypothermia, hypothermia, and post-hypothermia phases. RESULTS: Twenty-six neonates met the eligibility criteria for this study. Neonates with an abnormal MCA mean flow velocity (MFV) during the hypothermia phase had a higher risk of brain MRI abnormalities (77.8% vs. 22.2%, p = 0.017) and neonates with abnormal high MFV of MCA had higher MR scores of basal ganglia (p = 0.022). However, there were no statistical differences between abnormal MFV of MCA and brain MRI abnormalities during pre- and post-hypothermia phases. CONCLUSIONS: During therapeutic hypothermia, mean cerebral blood flow velocity of the MCA was associated with the severity of MRI brain injury in the neonates with clinical HIE.

Unusual Presentations of Birth Related Cervical Spinal Cord Injury.

Neonatal spinal cord injury is a rare complication of birth trauma by difficult delivery. The typical manifestations are often catastrophic, include decreased or absent movement, loss of reflexes, apnea or periodic breathing, and a lack of response to painful stimulation. The outcome is usually fatal or severe, with long-term sequelae of respiratory insufficiency, limb weakness, or even paralysis of the limbs. We described a male neonate with a C2 spinal cord injury who was born smoothly by vaginal delivery and was unnoticed initially due to unusual subtle symptoms. He presented with a hoarse voice, swallowing dysfunction, decreased movement of upper limbs, and hypercapnia. After receiving corticosteroid therapy and rehabilitation, he recovered much except that he still needed ventilator support at night.

A retrospective study on the incidence of acute kidney injury and its early prediction using troponin-I in cooled asphyxiated neonates.

Acute kidney injury (AKI) is a common complication of perinatal asphyxia and is associated with poorer short-term and long-term outcomes. This retrospective study describes the incidence of AKI in asphyxiated neonates who have received therapeutic hypothermia using the proposed modified Kidney Diseases: Improving Global Outcomes (KDIGO) definition and investigates clinical markers that would allow earlier recognition of at-risk neonates. We included asphyxiated  neonates who underwent therapeutic hypothermia between the period of January 2011 and May 2018 in our study. The serum creatinine levels within a week of birth were used in establishing AKI according to the modified KDIGO definition. Demographic data, resuscitation details, laboratory results and use of medications were collected and compared between the AKI and non-AKI groups to identify variables that differed significantly. A total of 66 neonates were included and 23 out of them (35%) were found to have AKI. The neonates with AKI had a lower gestational age (p = 0.006), lower hemoglobin level (p = 0.012), higher lactate level before and after therapeutic hypothermia (p = 0.013 and 0.03 respectively) and higher troponin-I level after therapeutic hypothermia (p < 0.001). After logistic regression analysis, elevated troponin-I after therapeutic hypothermia was independently associated with risk of AKI (OR 1.69, 95% CI 1.067-2.699, p = 0.025). The receiver operating curve showed that troponin-I after therapeutic hypothermia had an area under curve of 0.858 at the level 0.288 ng/ml. Our study concludes that the incidence of AKI among asphyxiated newborns who received therapeutic hypothermia is 35% and an elevated troponin-I level after therapeutic hypothermia is independently associated with an increased risk of AKI in asphyxiated newborns.

Seizures severity during rewarming can predict seizure outcomes of infants with neonatal hypoxic-ischemic encephalopathy following therapeutic hypothermia.

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.

Human cytomegalovirus pp65 peptide-induced autoantibodies cross-reacts with TAF9 protein and induces lupus-like autoimmunity in BALB/c mice.

Human cytomegalovirus (HCMV) has been linked to the triggering of systemic lupus erythematosus (SLE). We proposed that B cell epitope region of HCMV phosphoprotein 65 (HCMVpp65)422-439 mimics an endogenous antigen and initiates lupus-like autoimmunity. Amino acid homology between HCMVpp65422-439 and TAF9134-144 (TATA-box binding protein associated factor 9, TAF9) was investigated using a similarity search in NCBI protein BLAST program (BLASTP). A murine model was used to confirm their antigenicity and ability to induce lupus-like symptoms. HCMVpp65422-439 induced immune responses with the presence of specific antibodies against HCMVpp65422-439 and TAF9134-144, as well as anti-nuclear and anti-double-stranded (ds)DNA antibodies that are characteristic of SLE. In addition, the majority of HCMVpp65422-439 and TAF9134-144 immunized mice developed proteinuria, and their renal pathology revealed glomerulonephritis with typical abnormalities, such as mesangial hypercellularity and immune complex deposition. Immunoglobulin eluted from the glomeruli of HCMVpp65422-439 immunized mice showed cross-reactivity with TAF9134-144 and dsDNA. Increased anti-TAF9 antibody activity was also observed in the sera from SLE patients compared with healthy people and disease controls. Molecular mimicry between HCMVpp65 peptide and host protein has the potential to drive lupus-like autoimmunity. This proof-of-concept study highlights the mechanisms underlying the link between HCMV infection and the induction of SLE.

Shifting Valproic Acid to Levetiracetam in Women of Childbearing Age With Epilepsy: A Retrospective Investigation and Review of the Literature.

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.