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SARS-CoV-2 infections in children occasionally manifest with severe neurologic signs. We report a case series of life-threatening encephalopathy associated with SARS-CoV-2 in 25 children in Australia, Japan, Singapore, and Taiwan during February 2022-January 2024. All children had severe encephalopathy develop, characterized by rapidly progressive cerebral edema, conditions known as acute shock with encephalopathy and multiorgan failure or acute fulminant cerebral edema. Among the 25 patients, 22 (88%) eventually died; 11 (44%) children died within 24 hours of hospitalization. In addition, 18 (72%) had illness manifest with shock, and 14 (56%) had multiorgan failure develop within 6 hours of neurologic onset. Serum concentrations of cytokines/chemokines including interleukin 6 and tumor necrosis factor-α were significantly higher within 24 hours of onset than for controls. SARS-CoV-2-associated encephalopathy cases such as those described here represent an emerging neurologic crisis with high mortality rate resulting from rapidly progressive brain edema and multiorgan failure.

In this review, we summarize the clinical presentations of the acute stage of anti-N-methyl-d-aspartate (NMDA) receptor encephalitis and the neurocritical care strategy in intensive care units. Anti-NMDA receptor encephalitis has characteristic clinical features and is predominantly seen in young adults and children. Most patients have five stages of clinical presentation, including a prodromal phase, psychotic and/or seizure phase, unresponsive and/or catatonic phase, hyperkinetic phase, and gradual recovery phase. The clinical course usually begins with viral infection-like symptoms that last for up to 2 weeks (prodromal phase), followed by the rapid development of schizophrenia-like psychiatric symptoms and seizures (psychotic and seizure phase). Patients may have a decreased level of consciousness with central hypoventilation, frequently requiring mechanical ventilation. In the subsequent hyperkinetic phase, patients present with orofacial-limb dyskinesia and autonomic instability. Children with significant neurological symptoms of anti-NMDA receptor encephalitis should initially be managed in a pediatric intensive care unit. The acute critical presentations are, refractory seizures, autonomic dysfunction, hypoventilation, cardiac arrhythmia, and hyperkinetic crisis. Symptom-guided therapies and critical care are necessary in the acute stage to improve the prognosis.

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. Comparison of pregnancy outcomes with or without use antiepileptic drugs in pregnant women with epilepsy.

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.

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.

The Brief COPE Inventory has been proven as acceptable psychometric properties to examine coping strategies among cancer patients. However, most psychometric testing studies have been carried out in Western countries, raising concerns about the properties’ relevance and applicability in other cultural contexts. This study aimed to present psychometric properties of the Brief COPE in a sample of patients with advanced cancer in Indonesia. Specifically, we intended to examine the factorial structure and the measure’s validity and reliability. This study included 440 patients from the original study who completed the Indonesian version of Brief COPE. We used exploratory factor analysis and confirmatory factor analysis to assess factor structure and evaluate the structural model fit, respectively. Reliability was demonstrated by internal consistency represented by Cronbach’s alpha coefficient. The factor analysis identified a 21-items scale with 5-factors (avoidance, religion and acceptance, social support coping, problem solving and distraction). Confirmatory factor analysis demonstrated a good model fit. For the whole scale and its subscales Cronbach’s alpha coefficients were acceptable signifying good reliability. Convergent, divergent validity and contrast group comparison were evidenced by significant correlations among subscales and the other instruments used. This study shows that the Indonesian version of Brief COPE is a reliable and valid instrument to measure coping in advanced cancer patients and is ready for use amongst this population in the Indonesian cultural context.

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.

In this review, we summarize the general mechanisms of the ketogenic diet, and the application of a ketogenic diet in pediatric intensive care units for the neurological disorders of children and young infants. A ketogenic diet is a high-fat, low-carbohydrate, adequate-protein diet. It can alter the primary cerebral energy metabolism from glucose to ketone bodies, which involves multiple mechanisms of antiepileptic action, antiepileptogenic properties, neuro-protection, antioxidant and anti-inflammatory effects, and it is potentially a disease-modifying intervention. Although a ketogenic diet is typically used for the chronic stage of pharmacoresistant of epilepsy, recent studies have shown its efficacy in patients with the acute stage of refractory/super-refractory status epilepticus. The application of a ketogenic diet in pediatric intensive care units is a challenge because of the critical status of the patients, who are often in a coma or have a nothing by mouth order. Moreover, a ketogenic diet needs to be started early and sometimes through parenteral administration in patients with critical conditions such as refractory status epilepticus or febrile infection-related epilepsy syndrome. Animal models and some case reports have shown that the neuro-protective effects of a ketogenic diet can be extended to other emergent neurological diseases, such as traumatic brain injury and ischemic stroke.

We investigate the coupling effects between a double-resonance split-ring resonators (SRRs) design and the epsilon-near-zero (ENZ) guided mode of ultrathin indium tin oxide (ITO) films on second-harmonic generation (SHG). The optimized SRRs with an aspect ratio of 0.3 support a magnetic dipole (MD) resonance within the ENZ regime of ITO and a higher-order resonance at the SH frequency to achieve mode matching under cross-polarized excitation. The SRR-ITO coupled system (as opposed to the nanorod-ITO coupled system) was found to perform constructive (destructive) polarization interference between the nonlinear polarization currents at the upper hybridized modes (ω ) and the linear electric field at SH frequency (2ω ), resulting in a 1218-fold SHG enhancement outperformed than that of the nanorod-ITO coupled system, as predicted by overlap integral analysis. The measured SHG conversion efficiency for the SRR-ITO coupled system exceeds 10 at an excitation wavelength of 1,320 nm, corresponding to a one-order (two-order) of magnitude enhancement compared to the nanorod-ITO coupled system (Au/ITO film). These findings highlight the potential of the proposed hybrid metasurfaces for efficient cross-polarized nonlinear signal generation, paving the way for advanced applications such as light sources, modulators in integrated photonic circuits, and biological sensing.

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.