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.

Psychosocial stress in children with Tourette syndrome and chronic tic disorder.

BACKGROUND: This study aimed to understand the longitudinal relationship between psychosocial stress with tic exacerbation in children with Tourette syndrome (TS) and chronic tic disorder. METHODS: Consecutive ratings of tic severity as well as child and parental reports of psychosocial stress were obtained for 373 children (296 males, 77 females; mean age 9y 5mo; SD 3y 3mo) with TS and chronic tic disorder between January 2018 and December 2020. The Yale Global Tic Severity Scale (YGTSS) global severity score, total tic score, and impairment rating were calculated. The stressful events and YGTSS measurements were used and treated as time-varying variables in the analyses. Models that controlled for non-independence among the repeated observations using a random intercept and random slope model were employed. Each participant was treated as a random factor in the modelling. RESULTS: Family-related stress, personal relationship stress and school-related stress were independently associated with increasing YGTSS global severity, total tic score, and impairment rating over time. An increased number of stressful events were associated with increased severity of tics. CONCLUSION: Family, personal relationships, and school-related stress were consistently associated with the exacerbation of tics. Managing these stressful events is important in the treatment of TS and chronic tic disorder.

Application of Drug Testing Platforms in Circulating Tumor Cells and Validation of a Patient-Derived Xenograft Mouse Model in Patient with Primary Intracranial Ependymomas with Extraneural Metastases.

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

Cranial ultrasonographic screening findings among healthy neonates and their association with neurodevelopmental outcomes.

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

Is the Yale Global Tic Severity Scale a valid tool for parent-reported assessment in the paediatric population? A prospective observational study in Taiwan.

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

Application of Sonography in the Diagnosis and Follow-Up of Trapped Temporal Horn of Lateral Ventricle: Two Case Reports.

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

[Genetic analysis of family constellation for cochlear implant recipients].

GJB2, SLC26A4 (PDS) and mitochondrial DNA (mtDNA) have been associated with sensorineural hearing loss. In the present study, the clinical, genetic and molecular analysis of 14 cochlear implant recipients and their parents was studied from April 2006 to September 2007. Of the 14 subjects, 35.7% had gene mutations; 28.6% had homozygous GJB2 235delC mutation, whose parents carried heterozygous GJB2 235delC mutation; and 7.1% had mtDNA A1555G mutation, whose mother carried mtDNA A1555G mutation too. There was no SLC26A4 (PDS) mutation. These results strongly suggested that the mutation in GJB2 gene was a major cause of deafness in cochlear implant recipients and the mutation of mtDNA A1555G was another important cause. Genetic test of hot-spots and analysis of family constellation can offer an accurate genetic counseling to deaf family and reduce the incidence of hearing loss.

[Cochlear implantation with suprameatal approach in Chinese children].

OBJECTIVE: To investigate the technique of the suprameatal approach for cochlear implantation in Chinese profound sensory hearing loss children. METHODS: Suprameatal approach for cochlear implantation were used in 50 cases (total 53 ears) with profound sensory hearing loss from May 2005 to January 2007. The electrode was passed through the suprameatal tunnel and went between the incus and chorda tympani into the scala tympani. RESULTS: Electrodes were completely inserted in 51 ears. There were no postoperative complications in all cases. Although the long effect need to be observed, all cases received better hearing and speech development benefit from cochlear implantation in the follow-up period. Among the 50 cases, 26 had speech perception in the open condition; 18 patients could speak short sentences although not clearly; and 6 patients learned to speak individual words only. CONCLUSIONS: The suprameatal approach was found to be a simple and safe technique that does not need mastoidectomy and avoid endangering the facial nerve and the chorda tympani. It enables wide exposure of middle ear and is especially suitable for cases with narrow facial recess or anteriorly located facial nerve.