Cardiac MRI six months after the onset of multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19: A retrospective follow-up study.

BACKGROUND: In 2020, reports revealed cases called multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19 or multisystem inflammatory syndrome in children. A small proportion of patients suffer from persistent left ventricular dysfunction at discharge. The primary aim was to investigate if myocardial impairment persists during follow-up in these patients. METHODS: Children fulfilling the criteria for multisystem inflammatory syndrome in children with cardiac involvement hospitalized between December 2020 and February 2022 were included in this retrospective single centre study. Cardiac MRI was performed six months after the onset of symptoms to evaluate possible persistent myocardial damage. RESULTS: Fifteen patients (80% male) with a median age of 8 years (interquartile range 4.5 - 13.5 years) were included. Upon admission, eight patients (53%) presented with reduced left ventricular function, with a median left ventricular ejection fraction of 54% (interquartile range 49.5%-61.5%) on transthoracic echocardiography. Elevated levels of cardiac-specific markers were found in 14 patients (93%). Cardiac MRI was performed in 12 patients at a median of 190.5 days after the onset of symptoms. Nine patients (75%) had normal left ventricular function, with a median left ventricular ejection fraction of 59.45%, while the remaining patients showed mildly to moderately reduced values. None of the patients showed signs of late gadolinium enhancement, indicating the absence of persistent myocardial scarring. CONCLUSION: During a follow-up of 6.2 months, mild to moderate cardiac impairment was revealed in 25% of patients evaluated by cardiac MRI. Although a majority of patients do not show signs of cardiac impairment, close follow-ups should be performed in a proportion of patients.

Distinct molecular response patterns of activating STAT3 mutations associate with penetrance of lymphoproliferation and autoimmunity.

Germline STAT3 gain-of-function (GOF) mutations have been linked to poly-autoimmunity and lymphoproliferation with variable expressivity and incomplete penetrance. Here we studied the impact of 17 different STAT3 GOF mutations on the canonical STAT3 signaling pathway and correlated the molecular results with clinical manifestations. The mutations clustered in three groups. Group 1 mutants showed altered STAT3 phosphorylation kinetics and strong basal transcriptional activity. They were associated with the highest penetrance of lymphoproliferation and autoimmunity. Group 2 mutants showed a strongly inducible transcriptional reporter activity and were clinically less penetrant. Group 3 mutants were mostly located in the DNA binding domain and showed the strongest DNA binding affinity despite a poor transcriptional reporter response. Thus, the GOF effect of STAT3 mutations is determined by a heterogeneous response pattern at the molecular level. The correlation of response pattern and clinical penetrance indicates a significant contribution of mutation-determined effects on disease manifestations.

Education, school type and screen time were associated with overweight and obesity in 2930 adolescents.

AIM: This cross-sectional study analysed the influence of socio-economic factors on screen time, overweight and obesity. METHODS: We asked adolescents aged 10, 14 and 17 from 10 school types in urban and rural regions in Upper Austria to complete questionnaires from December 2012 to February 2013. Their parents were also asked to complete questionnaires. RESULTS: The questionnaires were completed by 2930 adolescents and 2209 parents. Total weekend screen time was significantly associated with a higher body mass index (BMI) in 10-year-old boys (p < 0.005) and 10-year-old girls (p = 0.002), and there were significant associations between higher BMI and television time and longer weekend video game use in subjects aged 10 and 14. Higher education levels were associated with shorter daily video game use and longer computer use. Males (p < 0.0001) and adolescents from immigrant families (p < 0.0001) reported longer screen times at all ages. Lower parental education and higher parental BMI correlated significantly with longer screen time and BMI in the youngest age group. CONCLUSION: The greatest weight problems were in younger adolescents, despite shorter screen times, and boys and adolescents from immigrant families reported the longest screen times. Prevention strategies need to start early.

Gender differences and the role of parental education, school types and migration on the body mass index of 2930 Austrian school children : A cross-sectional study.

BACKGROUND: Austria faces increasing numbers of childhood overweight and obesity. Despite increasing numbers of studies, associations between parental body mass index (BMI) and education and the school type on overweight/obesity in students have not been reported. The objective of this study was to evaluate the influence of these parameters on the genesis of overweight/obesity in a large cohort representative of youth in Upper Austrian. METHODS: A cross-sectional analysis of data from 2930 children and adolescents aged 10, 14 or 17 years from 11 different state school types was conducted. Students and their parents completed a questionnaire and heights and weights were measured. RESULTS: Of the students 16.9% fulfilled the criteria for overweight and 5.6% for obesity, with the highest rates in the 10-year-olds (19.6% and 5.8%, respectively). While no gender differences were present in the youngest age group, the body mass index (BMI) during adolescence remained higher in boys but decreased significantly in girls. Male gender remained a risk factor through all calculations. Boys were overrepresented in schools with lower education levels and more often had BMIs ≥ 85th and ≥95th percentile. Higher parental education levels and lower parental BMIs were associated with lower BMIs of their offspring. Migration was an additional association factor for BMIs ≥ 85th percentile. CONCLUSION: Low parental education levels, higher parental BMIs and migration background were associated with overweight and obesity in 10-year-olds. In adolescence, male gender and higher parental BMIs remained risk factors.

Fatal cerebral haemorrhage in a hypertensive seven-year-old boy.

A seven-year-old boy died from autopsy-proven brain haemorrhage due to hypertensive vasculopathy. This emphasizes the importance of early diagnosis and therapy of hypertension in children. Brain haemorrhage is a potentially fatal complication of paediatric hypertension.

Confirmation of Host Genetic Determinants in the CFH Region and Susceptibility to Meningococcal Disease in a Central European Study Sample.

BACKGROUND: Invasive meningococcal disease (IMD) is a leading cause of meningitis and severe sepsis in children and adolescents. Genetic factors are important in determining the susceptibility to and outcome of IMD. Recently, a genome-wide association study from the United Kingdom showed significant associations of single-nucleotide polymorphisms within complement factor H (CFH; rs1065489) and in CFH-related protein 3 (rs426736) with susceptibility of IMD. We report data of a genetic replication study in Central European children. METHODS: The study was conducted as a retrospective case-reference study involving 248 patients with confirmed diagnosis of IMD from Austria and Germany and 835 healthy reference individuals from a multicenter German birth cohort. RESULTS: Carriers of the minor alleles of rs1065489 and rs426736 were at lower risk of IMD [allelic odds ratio = 0.60 (0.44-0.82); P = 0.001 and 0.61 (0.45-0.83); P = 0.001]. Also, 2 major haplotypes (GT and TC) derived from the 2 single-nucleotide polymorphisms were significantly associated with IMD (P = 0.001 and P = 0.003, respectively). CONCLUSIONS: The consistency of the results between the genome-wide association study and our study population strengthens the association of CFH polymorphisms to the susceptibility of IMD. Our results support the conclusion that CFH is a critical determinant in acquiring meningococcal disease.

Prospective analysis on brain magnetic resonance imaging in children.

BACKGROUND: Previous studies have addressed the prevalence of incidental findings in adult populations. There are few studies following paediatric patients, most of data were retrieved retrospectively. We conducted a prospective study to determine the prevalence of incidental, pathologic and normal findings in a symptomatic paediatric population. METHODS: The subjects of this prospective single centre study are 436 children aged 0-18 years with clinical symptoms and subsequent first brain MRI. Normal, incidental as well as pathologic MRI findings are documented in association with age, gender, neurological examination and previous investigations (CCT, EEG). Secondary outcome parameters are defined as MRI results and their implications. Two board-certified radiologists prospectively analysed MR images without knowing the result from each other. RESULTS: The 436 patients with brain MRI were categorized into three groups as follows: 155 (35.5%) patients had normal findings, 163 (37.4%) had incidental findings and 118 (27.1%) had pathological findings in brain MRI. When adding patients with pathologic and incidental findings we report even more (47.9%). We analysed the correlation between neurologic examination and MRI result and it was significant (p-value 0.0008). The p-value for concordance of both radiology reports was <0.001 and therefore highly significant. CONCLUSION: To our knowledge this is the first prospective paediatric study reporting the prevalence of normal, pathologic and incidental findings in brain MRI in symptomatic children. Incidental findings are common in paediatric patients but we report the highest prevalence. Our data may help guiding management decision in a consistent and clinically appropriate manner.

Status epilepticus, cardiac resuscitation, and posterior reversible encephalopathy syndrome after ingestion of viscous lidocaine: a plea for more childproof packaging of pharmaceuticals.

Ingestion of viscous lidocaine in children can lead to potentially lethal neurologic and cardiac effects. We report the case of a 2-year-old boy who developed posterior reversible encephalopathy syndrome 2 days after unobserved ingestion of about 500 mg viscous lidocaine (40 mg/kg of bodyweight). Initially, the child presented with convulsive status epilepticus and subsequent cardiac arrest necessitating cardiopulmonary resuscitation for eight minutes. After 2 days of full recovery, the child presented with progressive disorientation, dizziness, and visual neglect. Lasting for 2 days, these symptoms finally disappeared completely. Combined with the findings on cerebral magnetic resonance imaging, this episode was interpreted as posterior reversible encephalopathy syndrome. Two weeks after the ingestion, no neurologic and visual abnormalities were found. Viscous lidocaine is prescribed routinely for dentition or other painful lesions in the oral cavity in children. Despite the potential hazardousness of the drug, packaging of viscous lidocaine is not childproof. Therefore, physicians have to instruct the parents carefully to minimize the risk of overuse or accidental ingestion. In general, the use of viscous lidocaine should be limited.

Facial nerve paralysis in children: is it as benign as supposed?

BACKGROUND: Facial nerve paralysis is a common disease in children. Most of the patients show complete recovery. This single-center cohort study exclusively included pediatric patients to investigate the outcome of all patients with facial nerve palsy. METHODS: Hospital records of all the patients admitted to the Children's Hospital in Linz between January 2005 and December 2010 with facial nerve paralysis were reviewed. Patients with peripheral facial nerve palsy were invited for clinical reevaluation between July 2011 and October 2011. The House-Brackmann score was used for reassessment. RESULTS: Fifty-six patients agreed to return for an additional clinical reevaluation. Study participants were divided in two groups according to their House-Brackmann scores: group 1 (n = 44), with a score <2 were considered good outcomes, and group 2 (n = 12), with a score ≥ 2 showed persistent mild to moderate dysfunction of the facial nerve and were considered moderate outcomes. The most important finding was the difference of the reported time to remission (P = 0.003) between the groups. CONCLUSION: The results of this study indicate that facial paralysis in children is not as benign as supposed. It is suggested that patients and their guardians be informed that a slight face asymmetry may persist, but functional recovery in general is excellent.

CD14 C-159T and toll-like receptor 4 Asp299Gly polymorphisms in surviving meningococcal disease patients.

BACKGROUND: Carriage of Neisseria meningitidis occurs approximately in 10% of the population, onset of invasive meningococcal disease (IMD) cannot be predicted and differs between ages. It remains unclear, which host factors determine invasion of the bloodstream by the bacteria. Innate immunity has a very important role in the first recognition of invading pathogens. The functional single nucleotide polymorphisms (SNPs) CD14 C-159T and toll-like receptor 4 (TLR4) Asp299Gly have been associated with the risk of gram-negative infections. However, their role in development of IMD still remains unclear. Our aim was to investigate the influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of IMD. METHODOLOGY/PRINCIPAL FINDINGS: It was a retrospective case control study. Surviving Austrian meningococcal disease patients were enrolled by sending buccal swabs for DNA analysis. 185 cases with a proven meningococcal infection and 770 healthy controls were enrolled. In surviving meningococcal disease patients DNA analysis of CD14 C-159T and TLR 4 Asp299Gly polymorphisms was performed, as they are part of the innate immune response to bacterial determinants. CD14 C-159T and TLR4 Asp299Gly SNPs were not significantly associated with the presence of IMD when compared to healthy controls. The odds ratio for CD14 C-159T SNP was 1.14 (95% confidence interval (CI) 0.91-1.43; p = 0.266). In TLR4 Asp 299 Gly SNP the odds ratio was 0.78 (CI 0.47-1.43; p = 0.359). CONCLUSION/SIGNIFICANCE: We could not observe a significant influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of developing IMD in surviving meningococcal disease patients. To our knowledge, this is the first study investigating the influence of the CD14 C-159T SNP on the susceptibility to IMD.

Aminoterminal brain-type natriuretic peptide levels correlate with heart failure in patients with bidirectional Glenn anastomosis and with morbidity after the Fontan operation.

OBJECTIVE: The aims of this study were to generate normal values of aminoterminal pro-brain natriuretic peptide in children with a bidirectional Glenn anastomosis without congestive heart failure and to test the hypothesis that plasma levels of aminoterminal pro-brain natriuretic peptide correlate with the clinical severity of congestive heart failure and morbidity after the Fontan operation. METHODS: Aminoterminal pro-brain natriuretic peptide plasma levels of 78 patients after the bidirectional Glenn operation with a median age of 3.2 years and a median follow-up time of 3 years were measured by using an automated enzyme immunoassay. The severity of heart failure was quantified by using the New York University Pediatric Heart Failure Index. RESULTS: The 97.5th percentile of aminoterminal pro-brain natriuretic peptide level in patients without congestive heart failure was 339 pg/mL. Aminoterminal pro-brain natriuretic peptide levels strongly correlated with the New York University Pediatric Heart Failure Index score (P < .001). In patients with congestive heart failure (31/78), the aminoterminal pro-brain natriuretic peptide levels were significantly higher (median, 670 pg/mL) than in patients without congestive heart failure (median, 171 pg/mL). In 41 patients who underwent the Fontan operation, the time to removal of chest tubes and the length of hospital stay positively correlated with the preoperative value of aminoterminal pro-brain natriuretic peptide. CONCLUSIONS: In children with a bidirectional Glenn anastomosis without signs of heart failure, aminoterminal pro-brain natriuretic peptide levels were within the normal range and correlated with the severity of congestive heart failure. Further studies are needed to determine whether aminoterminal pro-brain natriuretic peptide levels can aide clinicians in the early detection of congestive heart failure in this patient group.

Fatal Epstein-Barr virus encephalitis in a 12-year-old child: an underappreciated neurological complication?

BACKGROUND: A 12-year-old boy presented to a community hospital with fever, malaise and fatigue. A polymerase chain reaction test of the cerebrospinal fluid was positive for Epstein-Barr virus. Despite intensive care treatment and antiviral drugs, the patient died 1 month after his initial presentation. INVESTIGATIONS: Physical examination, polymerase chain reaction analysis of the cerebrospinal fluid, brain MRI, immunohistochemistry and molecular biological investigations of postmortem brain samples. DIAGNOSIS: Epstein-Barr Virus encephalitis. MANAGEMENT: Aciclovir, intensive care treatment with intubation, sedation, antiepileptic drugs.

Enema-induced severe hyperphosphatemia in children.

We report the case of a 13-year-old boy with Costello syndrome and chronic constipation who received phosphate-containing Fleet-pediatric enemas at regular intervals. The day before admission he was given four enemas for severe constipation. Within 24 h the boy had developed severe hyperphosphatemia (phosphate 17.75 mmol/L), hypertonic dehydration (sodium 171 mmol/L) and severe hypocalcemia (calcium 0.56 mmol/L). With early intervention and treatment, the child survived without sequelae. Osmotically acting hypertonic phosphate enemas may result in severe toxicity. Children with developmental delay often display bowel dysfunction and chronic constipation and are therefore high-risk patients. The accepted opinion-that these enemas are not absorbed and therefore systemically inactive-is not true. Physicians should be aware of the potentially lethal complications of this treatment, which is part of everyday clinical practice.

Vaccine strategies of meningococcal disease: results of a 10-year population-based study.

UNLABELLED: Invasive meningococcal disease (IMD) is an important cause of morbidity and mortality in children and adults. This study was conducted to determine a possible increase in IMD in recent years with special interest focused on serogroup C disease. From January 1st 1993 to December 31st 2002, IMD was studied in one million residents of Austria. We used active, population-based surveillance data from the Office of Public Health. A total of 126 patients with positive blood and/or cerebrospinal fluid culture or positive swabs for Neisseria meningitidis were studied. The median age of all patients was 9.5 years (range 1 month to 63 years). The average incidence of all IMD subgroups was 1.05 cases per 100,000 person years and was highest in children 0-4 years old (7.08 cases per 100,000 person years) followed by young adults aged 15 to 19 years (4.35 cases per 100,000 person years). Serogroup C IMD occurred in 1.30 cases/100,000 person years in patients aged 0 to 4 years and in 1.92 cases/100,000 person years in patients aged 15 to 19 years. Overall mortality was 11.1%. There was a significant increase (P =0.001) in IMD due to serogroup B disease within the last 10 years. In contrast, serogroup C disease did not increase during the last decade. CONCLUSION: Currently, we do not recommend mass vaccination against serogroup C disease in Austria, but young adults aged 15 to 19 years display a high incidence of meningococcal C disease. In this age group, vaccination against serogroup C disease should be considered.