Medication Overuse Headaches among Children-The Contribution of Migraine and TTH.

Medication overuse headaches are a frequent phenomenon observed in individuals suffering from chronic headaches. It arises due to the excessive consumption of pain-relief medications, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a retrospective study and analyzed the medical records of children and adolescents who were evaluated at the outpatient pediatric headache clinic at the Bnai Zion Medical Center for headaches during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients experiencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with migraine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with the undifferentiated headache of childhood, with the majority (73%) being female. In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pediatric cases, shedding light on its distinct characteristics in the realm of childhood headache disorders. Further research is warranted to elucidate the underlying factors contributing to the observed gender disparity and the distinct prevalence rates among different headache subtypes.

Danon Disease: Entire LAMP2 Gene Deletion with Unusual Clinical Presentation-Case Report and Review of the Literature.

Danon disease is a rare x-linked dominant multisystemic disorder with a clinical triad of severe cardiomyopathy, skeletal myopathy, and intellectual disability. It is caused by defects in the lysosome-associated membrane protein-2 (LAMP2) gene. Numerous different mutations in the LAMP2 protein have been described. Danon disease is typically lethal by the mid-twenties in male patients due to cardiomyopathy and heart failure. Female patients usually present with milder and variable symptoms. This report describes a 42-year-old father and his 3-year-old daughter presenting with mild manifestations of the disease. The father has normal intellectual development and normal physical activity. At the age of 13, he was diagnosed with mild ventricular pre-excitation known as Wolf-Parkinson-White syndrome (WPWs), very mild and mostly asymptomatic cardiomyopathy and left ventricular hypertrophy, and at about the age of 25 presented with visual impairment due to cone-rod dystrophy. His daughter showed normal development and very mild asymptomatic electrocardiographic WPWs abnormalities with left mild ventricular hypertrophy. Genetic testing revealed an Xq24 microdeletion encompassing the entire LAMP2 gene. Relevant literature was reviewed as a reference for the etiology, diagnosis, treatment and case management.

Intracardiac Thrombi in Preterm Infants-A Case Study and Review of the Literature.

Intracardiac thrombi in preterm infants are not common but may lead to fatal outcomes. Predisposing and risk factors include small vessel size, hemodynamic instability, immaturity of the fibrinolytic system, indwelling central catheters and sepsis. In this paper, we present our own experience with a case of a catheter-related right atrial thrombus in a preterm infant, which was successfully treated with an aspiration thrombectomy. Then, we review the literature on intracardiac thrombosis in preterm infants: epidemiology, pathophysiology, clinical signs, echocardiographic diagnostic features and treatment options are discussed.

The effect of patent ductus arteriosus on coronary artery blood flow in premature infants: a prospective observational pilot study.

OBJECTIVE: To compare coronary flows between premature infants with and without hemodynamically significant patent ductus arteriosus (hsPDA) and to determine if coronary flow is influenced by medical PDA treatment. DESIGN: Prospective, observational pilot study. Forty-three infants <32 weeks gestation underwent echocardiography when routinely indicated. Study group included infants with hsPDA requiring treatment. Comparison groups included infants with nonsignificant PDA and infants without PDA. RESULTS: The study group (n = 13), compared with the comparison groups with nonsignificant PDA (n = 12) and without PDA (n = 18) had higher troponin levels (p = 0.003 and 0.004, respectively). In infants with hsPDA compared with infants with no PDA there was a significant increase in myocardial oxygen demand and decrease in left main coronary artery flow, with nonsignificant increase in cardiac output. CONCLUSIONS: Decrease in coronary artery flows and higher troponin values may suggest a "steal effect," not allowing to meet the elevated myocardial oxygen demand in infants with hsPDA.

A Retrospective Study of the Impact of Pneumococcal Conjugate Vaccine-13 Immunization in a Northern Israel Hospital.

BACKGROUND: The introduction of pneumococcal conjugate vaccine-13 (PCV-13) has reduced the burden of invasive pneumococcal disease. OBJECTIVES: To characterize true positive blood cultures of children who presented to our hospital following implementation of the PCV-13 vaccine. METHODS: A retrospective study was conducted on positive blood cultures of children presenting with fever from 2010-2017. Subjects were divided into two age groups: a younger group 3-36 months and an older group 3-18 years. Patients were classified as either having or not having a focus of infection at the time of their bacteremia. Pneumococcal isolates were typed at Israel's Streptococcal Reference Laboratory. RESULTS: The samples included 94 true positive blood cultures. Focal infection with concomitant bacteremia was more common than bacteremia without a focus both overall: 67/94 (71%) vs. 27/94 (28.7%), P <0.001 as well as in the two groups: 32/48 (66%) vs. 16/48 (33%), P = 0.02 in the younger group and 35/46 (76%) vs. 11/46 (24%), P = 0.001 in the older group. Streptococcus pneumoniae was the most common pathogen overall, 27/94 (29%), and in the younger group, 21/48 (44%), but rare in the older group, 6/46 (13%). In the latter, Brucella species predominated, 12/46 (26%), along with Staphylococcus aureus 12/46 (26%). CONCLUSIONS: Our findings are consistent with other studies reporting decreased pneumococcal bacteremia, bacteremia primarily accompanying focal infection, and changing etiological agents among PCV-13-vaccinated children. Brucella species was prominent in older children with osteoarticular infections. Ongoing surveillance is warranted to better understand the implications of PCV-13.

Validation of a Novel Assay to Distinguish Bacterial and Viral Infections.

BACKGROUND: Reliably distinguishing bacterial from viral infections is often challenging, leading to antibiotic misuse. A novel assay that integrates measurements of blood-borne host-proteins (tumor necrosis factor-related apoptosis-inducing ligand, interferon γ-induced protein-10, and C-reactive protein [CRP]) was developed to assist in differentiation between bacterial and viral disease. METHODS: We performed double-blind, multicenter assay evaluation using serum remnants collected at 5 pediatric emergency departments and 2 wards from children ≥3 months to ≤18 years without (n = 68) and with (n = 529) suspicion of acute infection. Infectious cohort inclusion criteria were fever ≥38°C and symptom duration ≤7 days. The reference standard diagnosis was based on predetermined criteria plus adjudication by experts blinded to assay results. Assay performers were blinded to the reference standard. Assay cutoffs were predefined. RESULTS: Of 529 potentially eligible patients with suspected acute infection, 100 did not fulfill infectious inclusion criteria and 68 had insufficient serum. The resulting cohort included 361 patients, with 239 viral, 68 bacterial, and 54 indeterminate reference standard diagnoses. The assay distinguished between bacterial and viral patients with 93.8% sensitivity (95% confidence interval: 87.8%-99.8%) and 89.8% specificity (85.6%-94.0%); 11.7% had an equivocal assay outcome. The assay outperformed CRP (cutoff 40 mg/L; sensitivity 88.2% [80.4%-96.1%], specificity 73.2% [67.6%-78.9%]) and procalcitonin testing (cutoff 0.5 ng/mL; sensitivity 63.1% [51.0%-75.1%], specificity 82.3% [77.1%-87.5%]). CONCLUSIONS: Double-blinded evaluation confirmed high assay performance in febrile children. Assay was significantly more accurate than CRP, procalcitonin, and routine laboratory parameters. Additional studies are warranted to support its potential to improve antimicrobial treatment decisions.

Sequence variation in PPP1R13L results in a novel form of cardio-cutaneous syndrome.

Dilated cardiomyopathy (DCM) is a life-threatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab Christian infants, aged 4-30 months from four families, were diagnosed with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3. A homozygous sequence variation creating a premature stop codon at PPP1R13L encoding the iASPP protein was identified in three infants and in the mother of the other two. Patients' fibroblasts and PPP1R13L-knocked down human fibroblasts presented higher expression levels of pro-inflammatory cytokine genes in response to lipopolysaccharide, as well as Ppp1r13l-knocked down murine cardiomyocytes and hearts of Ppp1r13l-deficient mice. The hypersensitivity to lipopolysaccharide was NF-κB-dependent, and its inducible binding activity to promoters of pro-inflammatory cytokine genes was elevated in patients' fibroblasts. RNA sequencing of Ppp1r13l-knocked down murine cardiomyocytes and of hearts derived from different stages of DCM development in Ppp1r13l-deficient mice revealed the crucial role of iASPP in dampening cardiac inflammatory response. Our results determined PPP1R13L as the gene underlying a novel autosomal-recessive cardio-cutaneous syndrome in humans and strongly suggest that the fatal DCM during infancy is a consequence of failure to regulate transcriptional pathways necessary for tuning cardiac threshold response to common inflammatory stressors.

Morphologic, mechanical, conductive, and hemodynamic changes following transcatheter closure of atrial septal defect.

OBJECTIVE: The secundum type of atrial septal defect (ASD) is a common congenital cardiac anomaly. Transcatheter closure of the defect is the preferable therapeutic approach to avoid potential future complications. This work extends the data collected so far regarding the electrocardiographic, morphologic, hemodynamic, and mechanical changes following the procedure. DESIGN: From April 2002 to October 2003, 42 consecutive patients underwent successful transcatheter closure of secundum type ASD. They were sampled for different parameters by transthoracic echocardiography before the procedure and at three different points over the next 4 years, and analyzed in two age groups: children and adults. RESULTS: The dimensions of the chambers normalized throughout the study period. Abnormal movement of the interventricular septum normalized mostly during the first month, but its thickness increased gradually to normal levels during the 4 years of the study. High elevated pulmonary artery pressure values began declining to near normal levels from the second month following the procedure. The stroke volume and the right bundle branch block pattern improved throughout the study period. CONCLUSIONS: Transcatheter ASD closure is followed by morphologic, conductive, and hemodynamic changes at different time intervals during the first years and results in normalization or near normalization of the heart's structure and function.

Transcatheter closure of right-to-left interatrial shunts to resolve hypoxemia.

BACKGROUND: Right-to-left interatrial shunts through an atrial septal defect or patent foramen ovale may result from congenital and acquired conditions. Right-to-left shunts may occur with normal pulmonary artery pressure and resistance as in right ventricular outflow tract obstruction leading to hypertrophy and reduced diastolic function, in right ventricle ischemia, myocarditis or cardiomyopathy and in orthodeoxia-platypnea syndrome. METHODS: We have tested the tolerance of trans-catheter closure of right-to-left interatrial shunts in 5 selected patients in whom the morphology and hemodynamics implied that it would be well-tolerated and improve functional capacity. Right-to-left shunt was demonstrated in 5 profoundly cyanotic patients by trans-thoracic and trans-esophageal echocardiography with intravenous injection of agitated saline. The patients were catheterized for hemo-dynamic study and tested for tolerance of transient balloon occlusion of the defects. RESULTS: Diastolic right ventricular dysfunction with elevated end-diastolic pressure was the primary cause of right-to-left shunt. Most shunts occur via atrial septal defects. Patients' ability to tolerate temporary balloon occlusion of the defects predicted a favorable outcome following permanent device occlusion. Cyanosis resolved in all patients following closure of the defects without congestive right heart failure. A marked improvement in functional capacity was observed in 4 patients. One died of preinterventional hypoxic brain damage. CONCLUSION: Transcatheter closure of right-to-left shunts is well-tolerated and a rewarding approach. It should be applied in selected patients following careful morphologic and hemodynamic evaluation. Tolerance of temporary occlusion of the defect is predictive of a favorable procedural outcome.

The familial form of atrial septal defect.

BACKGROUND: The secundum atrial septal defect accounts for 10% of congenital heart disease. Familial occurrence is rare and may present as an isolated lesion or with conduction and skeletal abnormalities. Predisposing genes were described. OBJECTIVES: To evaluate familial defect's prevalence and associated anomalies and assess the yield of screening. METHODS: Family history, physical, electrocardiographic and echocardiographic evaluation of 286 ASD patients and families regarding heart disease, conduction and skeletal anomalies were performed. RESULTS: Eleven new families with familial defects were identified yielding 28 patients. The rate of transmission was 40-100%, suggestive of autosomal dominant inheritance. Parents were healthy in four families with multiple offspring with ASDs. Two families had ASDs with atrioventricular conduction abnormalities in five of six subjects, not requiring pacing. One subject had skeletal malformation. Ten patients had surgery, 12 had transcatheter ASD closure and six await treatment. CONCLUSIONS: In view of the high prevalence of familial occurrence of secundum ASD (10% of all ASD patients), we recommend screening all first degree relatives of ASD patients for cardiac, conduction and skeletal anomalies. Although a routine genetic investigation is not yet available, genetic patterns of inheritance may be compatible with autosomal dominant inheritance. Healthy parents of affected offspring may suggest a variable gene penetrance or past spontaneous ASD closure. Conduction anomalies may be present or may develop throughout life, and thus should be periodically screened for.

Anomalous origin of the main stem of the left coronary artery from the pulmonary trunk presenting with left ventricular hypertrophy.

Patients with anomalous origin of the left coronary artery from the pulmonary trunk may present with paroxysmal angina on exertion, congestive heart failure, dyspnoea, syncope or sudden death. The association of such anomalous origin of the left coronary artery from the pulmonary trunk with a hypertrophic left ventricle is extremely rare. In our cohort of patients with anomalous origin of the left coronary artery from the pulmonary trunk, two presented with a hypertrophic left ventricle. We discuss these cases, accompanied by a review of the English literature describing different morphological anomalies of the coronary arteries associated with left ventricular hypertrophy. Whether the hypertrophy is a result of the evolvement of the collateral coronary system, or due to an additional pathological gene for hypertrophic obstructive cardiomyopathy, remains an enigma. The hypertrophy may have served as a compensatory mechanism accounting for the atypical clinical presentation. We further discuss the possible factors associating the occurrence of anomalous origin of the left coronary artery from the pulmonary trunk and myohypertrophy, supported by the documentation of the regression of hypertrophy following surgical correction of the anomalous arterial origin as seen in our patients.

The surgical manifestations of the intestinal tract in Kawasaki disease.

Kawasaki disease (KD) is an inflammatory condition of unknown etiology. It involves mainly the skin, mucous membranes, lymph nodes, and myocardium. It may involve the gastrointestinal tract; however, it rarely presents as a surgical abdomen. We present a case of a young child with suspected small bowel obstruction who was subsequently diagnosed with KD. We review the surgical presentations of the intestinal tract in KD.