Neurological manifestations of SARS-CoV-2 infection in children in Taiwan: A cross-section, multicenter study.

BACKGROUND: The SARS-CoV-2 virus has been a global public health threat since December 2019. This study aims to investigate the neurological characteristics and risk factors of coronavirus disease 2019 (COVID-19) in Taiwanese children, using data from a collaborative registry. METHODS: A retrospective, cross-sectional, multi-center study was done using an online network of pediatric neurological COVID-19 cohort collaborative registry. RESULTS: A total of 11160 COVID-19-associated emergency department (ED) visits and 1079 hospitalizations were analyzed. Seizures were the most common specific neurological symptom, while encephalitis and acute disseminated encephalomyelitis (ADEM) was the most prevalent severe involvement. In ED patients with neurological manifestations, severe neurological diagnosis was associated with visual hallucination, seizure with/without fever, behavior change, decreased GCS, myoclonic jerk, decreased activity/fatigue, and lethargy. In hospitalized patients with neurological manifestations, severe neurological diagnosis was associated with behavior change, visual hallucination, decreased GCS, seizure with/without fever, myoclonic jerk, fatigue, and hypoglycemia at admission. Encephalitis/ADEM was the only risk factor for poor neurological outcomes at discharge in hospitalized patients. CONCLUSION: Neurological complications are common in pediatric COVID-19. Visual hallucination, seizure, behavior change, myoclonic jerk, decreased GCS, and hypoglycemia at admission are the most important warning signs of severe neurological involvement such as encephalitis/ADEM.

Randomized Controlled Trial of Probiotic PS128 in Children with Tourette Syndrome.

Tourette syndrome results from a complex interaction between social-environmental factors, multiple genetic abnormalities, and neurotransmitter disturbances. This study is a double-blinded, randomized controlled trial using probiotics Lactobacillus plantarum PS128 as an intervention to examine if probiotics improve symptoms of children with Tourette syndrome. This study enrolled children aged 5 to 18 years old who fulfilled DSM-V diagnostic criteria for Tourette syndrome. Patients were assessed before initiating the trial, at one month, and at two months after randomization. The primary outcome was evaluated by Yale Global Tic Severity Scale (YGTSS), and the secondary outcome studied the possible comorbidities in these children. The results revealed no significant difference in improvement in YGTSS between the control group and the PS128 group. As for secondary endpoints, an analysis of Conners' Continuous Performance Test (CPT) showed improvement in commission and detectability in the PS128 group. In conclusion, although probiotics may not have tic-reducing effects in children with Tourette syndrome, it may have benefits on comorbidities such as attention deficit and hyperactivity disorder (ADHD). Further studies are needed to clarify the effects of probiotics on the comorbidities of Tourette syndrome children.

Intracerebral large artery disease in Aicardi-Goutières syndrome with TREX1 mutation: a case report.

We report a patient diagnosed with Aicardi-Goutières syndrome (AGS) with homozygous TREX1 gene mutation. Her magnetic resonance angiography (MRA) showed intracerebral large artery disease, which was rarely reported in the past in TREX1 AGS patients. Her younger sister also had homozygous TREX1 gene mutation and died of necrotizing enterocolitis. Intracerebral large artery involvement has been seen as a particular feature of SAMHD1-related disease. Our patient also had arthropathy, which is a finding more commonly mentioned in SAMHD1-related diseases. The observations in our case may contribute to our understanding of the pathogenetic mechanism of TREX1 AGS, involving the intracerebral large arteries, arthropathy, and possibly the gastrointestinal tract.

The role of targeted gene panel in pediatric drug-resistant epilepsy.

About 10-30% of pediatric patients with epilepsy have drug-resistant epilepsy. Genetic panels may be useful in identifying etiology and guiding treatment in pediatric patients with drug-resistant epilepsy. In our tertiary center, we used two epilepsy panels, an initial 24-genes panel followed by a more comprehensive 122-genes panel to screen for genetic cause over recent 2 years. A total of 96 patients with drug-resistant epilepsy were evaluated using the 24-genes panel, which revealed 10 (10.4%) of the patients with pathogenic variants. Another 22 patients without causative genetic variants using first-gene panel were evaluated using the 122-genes panel. Out of the 22 patients, 4 had pathogenic variants, and 6 had variants of unknown significance. The total yield rate for the second panel was 18.2% (4/22). In conclusion, although whole exome sequencing has entered clinical practice, epilepsy gene panels may still play some roles because of lower cost and faster time, especially in those with fever-associated epilepsy.

Novel Anthranilic Diamide Scaffolds Containing N-Substituted Phenylpyrazole as Potential Ryanodine Receptor Activators.

To discover potent insecticides targeting ryanodine receptors (RyRs), a series of novel anthranilic diamides analogues (12a-12u) containing N-substituted phenylpyrazole were designed and synthesized. These compounds were characterized by (1)H NMR, (13)C NMR, and HRMS, and the structure of compound 12u was confirmed by X-ray diffraction. Their insecticidal activities indicated that these compounds displayed moderate to excellent activities. In particular, 12i showed 100 and 37% larvicidal activities against oriental armyworm (Mythimna separata) at 0.25 and 0.05 mg L(-1), equivalent to that of chlorantraniliprole (100%, 0.25 mg L(-1); and 33%, 0.05 mg L(-1)). The activity of 12i against diamondback moth (Plutella xylostella) was 95% at 0.05 mg L(-1), whereas the control was 100% at 0.05 mg L(-1). The calcium-imaging technique experiment results showed that the effects of 12i on the intracellular calcium ion concentration ([Ca(2+)]i) in neurons were concentration-dependent. After the central neurons of Helicoverpa armigera were dyed by loading with fluo-5N and treated with 12i, the free calcium released in endoplasmic reticulum indicated the target of compound 12i is RyRs or IP3Rs. The activation of RyRs by natural ryanodine completely blocked the calcium release induced by 12i, which indicated that RyRs in the central neurons of H. armigera third-instar larvae is the possible target of compound 12i.