Let's get physical: Aerobic capacity, muscle strength, and muscle endurance after pediatric heart transplantation.

BACKGROUND: Pediatric heart (HTx) and kidney transplant (KTx) recipients may have lower physical fitness than healthy children. This study sought to quantify fitness levels in transplant recipients, investigate associations to clinical factors and quality of life, and identify whether a quick, simple wall-sit test is feasible as a surrogate for overall fitness for longitudinal assessment. METHODS: Aerobic capacity (6-min walk test, 6MWT), normalized muscle strength, muscle endurance, physical activity questionnaire (PAQ), and quality of life (PedsQL™) were prospectively assessed in transplanted children and matched healthy controls. RESULTS: Twenty-two HTx were compared to 20 controls and 6 KTx. 6MWT %predicted was shorter in HTx (87.2 [69.9-118.6] %) than controls (99.9 [80.4-120] %), but similar to KTx (90.3 [78.6-115] %). Muscle strength was lower in HTx deltoids (6.15 [4.35-11.3] kg/m2) and KTx quadriceps (9.27 [8.65-19.1] kg/m2) versus controls. Similarly, muscle endurance was lower in HTx push-ups (28.6 [0-250] %predicted), KTx push-ups (8.35 [0-150] %predicted), HTx curl-ups (115 [0-450] %predicted), and KTx wall-sit time (18.5 [10.0-54.0] s) than controls. In contrast to HTx with only 9%, all KTx were receiving steroid therapy. The wall-sit test significantly correlated with other fitness parameters (normalized quadriceps strength R = .31, #push-ups R = .39, and #curl-ups R = .43) and PedsQL™ (R = .36). CONCLUSIONS: Compared to controls, pediatric HTx and KTx have similarly lower aerobic capacity, but different deficits in muscle strength, likely related to steroid therapy in KTx. The convenient wall-sit test correlates with fitness and reported quality of life, and thus could be a useful easy routine for longitudinal assessment.

DNA major versus minor groove occupancy of monomeric and dimeric crystal violet derivatives. Toward structural correlations.

Six monomeric (1a-1f) and five dimeric (2a-2e) derivatives of the triphenylmethane dye crystal violet (CV) have been prepared. Evaluation of the binding of these compounds to CT DNA by competitive fluorescent intercalator displacement (FID) assays, viscosity experiments, and UV and CD spectroscopy suggest that monomeric derivative 1a and dimeric derivative 2d likely associate with the major groove of DNA, while dimeric derivatives 2a and 2e likely associate with the minor groove of DNA. Additional evidence for the groove occupancy assignments of these derivatives was obtained from ITC experiments and from differential inhibition of DNA cleavage by the major groove binding restriction enzyme BamHI, as revealed by agarose gel electrophoresis. The data indicate that major groove ligands may be optimally constructed from dye units containing a sterically bulky 3,5-dimethyl-N,N-dimethylaniline group; furthermore, the groove-selectivity of olefin-tethered dimer 2d suggests that stereoelectronic interactions (n â†’ π*) between the ligand and DNA are also an important design consideration in the crafting of major-groove binding ligands.

Successful ABO incompatible heart transplantation after desensitization therapy in an older child.

BACKGROUND: ABO-incompatible heart transplantation (HTx) has become a standard procedure for children below 2 years of age due to an immunologically immature immune system and associated low isohemagglutinin titers. METHODS: We report a case of an ABO-incompatible HTx (recipient blood group O, donor blood group A) at the age of 5 years and 11 months with a fully matured immune system and previously high isohemagglutinin titers that diminished as a result of human leucocyte antigen (HLA) desensitization therapy with rituximab and immunoglobulins. RESULTS: The anti-A titer at the time of HTx was 1:16 with post-transplant isoagglutinin titers never exceeding 1:4 without any signs of rejection with now 3 years of post-HTx follow-up. CONCLUSIONS: ABO isohemagglutinin titers should be routinely assessed in children undergoing desensitization therapy since ABOi transplantation can be considered in selected cases to expand the donor pool with the option of crossing the ABO barrier to find a better-matched allograft.

Practice Patterns in the Management of Pressure Restrictive Perimembranous Ventricular Septal Defects: A Multinational Survey.

Indications for the closure of pressure restrictive perimembranous ventricular septal defects (pmVSD) are not well established in the pediatric population. We sought to assess practice variability among pediatric cardiologists in the United States (US), Canada, Australia, and New Zealand. A survey ascertaining practice patterns, including case vignettes with incremental progression of disease severity, was designed and administered through representative professional cardiac organizations and email listservs in the designated countries. Among the 299 respondents, 209 (70.0%) were from the US, 65 (21.7%) were from Canada and 25 (8.3%) were from Australia and New Zealand. Indications for pressure restrictive pmVSD closure included the presence of left ventricular (LV) dilation for 81.6% (244/299) (defined as z-score ≥ 2 for 59.0% (144/244) and ≥ 3 for 40.2% (98/244)) and significant pulmonary-systemic flow ratio (QP:QS) for 71.2% (213/299) [defined as ≥ 1.5:1 for 36.2% (77/213) and ≥ 2 for 62% (132/213)]. US pediatric cardiologists elected to close restrictive pmVSD at lower LV z-score and QP:QS ratio cut-offs (p-value 0.0002 and 0.013, respectively). In a case vignette, 63.6% (173/272) chose to intervene if there was right coronary cusp prolapse with stable mild aortic regurgitation. Of the remaining cardiologists, 93% (92/99) intervened if the aortic regurgitation was progressive (from trivial to mild). Commonly identified indications with variable thresholds for closure of pressure restrictive pmVSDs included the presence or progression of LV dilation, significant volume loading, and aortic valve prolapse with regurgitation. US pediatric cardiologists may have a lower threshold for pmVSD closure.

COVID-19 Positive Versus Negative Complete Kawasaki Disease: A Study from the International Kawasaki Disease Registry.

To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID-; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID- and 61 were KDCOVID+. KDCOVID+ patients were older (median 5.5 vs. 3.7 years; p < 0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p = 0.008) and headache (38% vs. 10%; p < 0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+ patients were more likely to have shock (41% vs. 6%; p < 0.001), ICU admission (62% vs. 10%; p < 0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p < 0.001), and to have received inotropic support (60% vs. 10%; p < 0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p = 0.63), but KDCOVID+ were more likely to have received steroids (85% vs. 35%; p < 0.001) and anakinra (60% vs. 10%; p = 0.002). KDCOVID- patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p = 0.01). KDCOVID+ patients differ from KDCOVID-, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.

Cardiac Biomarkers Aid in Differentiation of Kawasaki Disease from Multisystem Inflammatory Syndrome in Children Associated with COVID-19.

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

Prevalence Implications of the 2017 American Academy of Pediatrics Hypertension Guideline and Associations with Adult Hypertension.

OBJECTIVE: To evaluate the impact of the 2017 American Academy of Pediatrics hypertension Clinical Practice Guideline (CPG), compared with the previous guideline ("Fourth Report"), on the frequency of hypertensive blood pressure (BP) measurements in childhood and associations with hypertension in adulthood using data from the International Childhood Cardiovascular Cohort Consortium. STUDY DESIGN: Childhood BPs were categorized in normal, prehypertensive/elevated, and hypertensive (stage 1 and 2) ranges using the Fourth Report and the CPG. Participants were contacted in adulthood to assess self-reported hypertension. The associations between childhood hypertensive range BPs and self-reported adult hypertension were evaluated. RESULTS: Data were available for 34 014 youth (10.4 ± 3.1 years, 50.6% female) with 92 751 BP assessments. Compared with the Fourth Report, the CPG increased hypertensive readings from 7.6% to 13.5% and from 1.3% to 2.5% for stage 1 and 2 hypertensive range, respectively (P < .0001). Of 12 761 adults (48.8 ± 7.9 years, 43% male), 3839 (30.1%) had self-reported hypertension. The sensitivity for predicting adult hypertension among those with hypertensive range BPs at any point in childhood, as defined by the Fourth Report and the CPG, respectively, was 13.4% and 22.4% (specificity 92.3% and 85.9%, P < .001), with no significant impact on positive and negative predictive values. Associations with self-reported adult hypertension were similar and weak (c-statistic range 0.61-0.68) for hypertensive range BPs as defined by the Fourth Report and CPG. CONCLUSIONS: The CPG significantly increased the prevalence of childhood BPs in hypertensive ranges and improved the sensitivity, without an overall strengthened association, of predicting self-reported adult hypertension.

Estimating nutritional needs in paediatric heart failure: beyond the equations.

BACKGROUND: Nutrition optimisation is imperative in paediatric patients with heart failure. Energy needs can be assessed using indirect calorimetry. METHODS: Presented are two cases of children with clinical heart failure who benefited from indirect calorimetry. RESULTS: Using indirect calorimetry, it was determined both cases were hypermetabolic. CONCLUSION: These cases demonstrate the impact of heart failure on metabolic rate and growth. Energy requirements were up to two times higher than estimations from predictive equations.

Use of Bedside Entertainment and Relaxation Theater (BERT) to Reduce Fear and Anxiety Associated With Outpatient Procedures in Pediatric Orthopaedics.

BACKGROUND: The aim of the present study was to evaluate the effectiveness of the Bedside Entertainment and Relaxation Theater (BERT) on fear, anxiety, and pain outcomes in pediatric orthopaedic patients associated with cast removal and/or pin removal in the outpatient clinic setting. METHODS: A total of 66 pediatric patients between the ages of 2 and 6 undergoing clinic procedures were recruited for this study and randomized into the control group or the intervention (BERT) group. Patients in the control group received standard of care during the cast room procedure; patients in the BERT group were given headphones and watched a movie on a projector during the procedure. Fear, anxiety, and pain were measured before and after the procedure. Procedures included cast removal, pin removal, or a combination of the 2. RESULTS: Patients in the BERT group reported less fear and anxiety overall after the procedure than patients in the control group (P=0.009, 0.015). Adjusting for procedure type (ie, pin removal), patients in the BERT group reported a 0.67 point decrease (95% confidence interval: 0.04, 1.30) on the fear scale after the procedure (P=0.039) and a 1.81 point decrease (95% confidence interval: 0.04, 3.59) on the anxiety scale associated with the procedure (P=0.045), compared with the control group. Patients and caregivers reported high satisfaction with BERT. CONCLUSION: This randomized, controlled trial demonstrates an evidence-based distraction tool that can be implemented across medical centers for pediatric patients undergoing office based orthopaedic procedures. BERT can be used to reduce fear and anxiety associated with these procedures, and increase patient and parent satisfaction. LEVEL OF EVIDENCE: Level I.

Total Syntheses and Absolute Configuration Assignment of (+)-Sootepdienone, (-)-Jambolanin C, (-)-Jambolanin I, and (-)-Gibberodione.

Total syntheses of the sesquiterpenes (+)-sootepdienone, (-)-jambolanin C, (-)-jambolanin I, and (-)-gibberodione have been accomplished in 10 steps each from R-(+)-pulegone, allowing assignment of the absolute configuration of the natural products. A key step in the synthetic pathways involves the one-carbon ring expansion of a cyclic allylic phosphonate to a substituted cycloheptenone by a tandem oxidative cleavage/intramolecular Horner-Wadsworth-Emmons reaction.

Hypertension masquerading as Pediatric Cardiomyopathy: an exercise in cognitive biases.

Heuristics and cognitive biases constantly influence clinical decision-making and often facilitate judgements under uncertainty. They can frequently, however, lead to diagnostic errors and adverse outcomes, particularly when considering rare disease processes that have common, masquerading presentations. Herein, we present two such cases of newborn infants with hypertensive renal disorders that were initially thought to have cardiomyopathy.

Risk factors and lifelong impact of community-acquired pneumonia in congenital heart disease.

INTRODUCTION: The prevalence of congenital heart disease (CHD) in adults is rising necessitating a greater understanding of acquired diseases such as community-acquired pneumonia, which remains a leading cause of age-related mortality and morbidity in the general population. We hypothesise that the CHD population, given cardiopulmonary mechanics and altered immune function, bears a uniquely high risk for pneumonia-related hospitalisations and mortality. METHODS: A countrywide cohort study was performed to calculate the relative risk and cumulative incidence of pneumonia hospitalisations and resultant 30-day mortality amongst the adult CHD population, matched 1:10 with non-CHD persons by gender, age, and adjusted for comorbidities. Cox proportional hazard regression quantified the impact of CHD severity and extracardiac defects. RESULTS: The CHD cohort includes 17,162 adults. The majority demonstrate mild/moderate CHD complexity. The cumulative incidence of pneumonia hospitalisation was higher for adults with CHD (hazard ratio 1.90; 95% confidence interval: 1.74-2.06) than the comparison cohort. This risk was increased for those with extracardiac defects or a syndrome (hazard ratio: 4.34; 95% confidence interval: 3.39-5.54). Additionally, CHD individuals with severe/univentricular subtypes demonstrate a heightened risk compared to the non-CHD cohort (hazard ratio: 2.35; 95% confidence interval: 1.94-2.84), as well as compared to those with mild/moderate CHD (hazard ratio: 1.28; 95% confidence interval: 1.07-1.53). In addition, pneumonia hospitalisation mortality was elevated above the comparison population with a 30-day mortality rate ratio of 1.31 (95% confidence interval: 1.00-1.73). CONCLUSION: Adults with CHD are at elevated risk of pneumonia hospitalisations and pneumonia-associated mortality. This risk is further elevated in those with severe CHD and extracardiac defects.

Virtual reality during pediatric vascular access: A pragmatic, prospective randomized, controlled trial.

BACKGROUND: Vascular access is a minor procedure that is associated with reported pain and fear in pediatric patients, often resulting in procedural incompliance. Virtual reality has been shown to be effective in adult populations for reducing pain and anxiety in various medical settings, although large studies are lacking in pediatrics. AIMS: The primary aim was to determine whether pain would be reduced in pediatric patients using virtual reality undergoing vascular access. The four secondary aims measured patient fear, procedural compliance, satisfaction, and adverse events. METHODS: A prospective, randomized, controlled trial was completed at a pediatric hospital, enrolling children 7-18 years old undergoing vascular access in a variety of clinical settings, randomized to virtual reality or standard of care. Pain scores were measured using a numeric pain faces scale. The secondary outcomes of patient fear, procedural compliance, satisfaction, and adverse events were measured with the Child Fear Scale, modified Induction Compliance Checklist, and satisfaction surveys, respectively. Chi-squared, t tests, and regression models were used to analyze the results. RESULTS: The analysis included 106 patients in the virtual reality group and 114 in the control. There were no significant differences in postprocedure pain (VR group estimated 0.11 points lower, 95% confidence interval: 0.50 points lower to 0.28 points greater, P = .59), postprocedure fear (VR group estimated 0.05 points lower, 95% confidence interval: 0.23 points lower to 0.13 points greater), or compliance (adjusted odds ratio 2.31, 95% confidence interval: 0.96-5.56). Children in the virtual reality group were satisfied with the intervention. There were no adverse events. CONCLUSION: This study demonstrates no reduction in pain while using Virtual reality (VR) across a heterogeneous pediatric inpatient population undergoing vascular access.

Cardiac rehabilitation in the paediatric Fontan population: development of a home-based high-intensity interval training programme.

INTRODUCTION: We evaluated the safety and feasibility of high-intensity interval training via a novel telemedicine ergometer (MedBIKE™) in children with Fontan physiology. METHODS: The MedBIKE™ is a custom telemedicine ergometer, incorporating a video game platform and live feed of patient video/audio, electrocardiography, pulse oximetry, and power output, for remote medical supervision and modulation of work. There were three study phases: (I) exercise workload comparison between the MedBIKE™ and a standard cardiopulmonary exercise ergometer in 10 healthy adults. (II) In-hospital safety, feasibility, and user experience (via questionnaire) assessment of a MedBIKE™ high-intensity interval training protocol in children with Fontan physiology. (III) Eight-week home-based high-intensity interval trial programme in two participants with Fontan physiology. RESULTS: There was good agreement in oxygen consumption during graded exercise at matched work rates between the cardiopulmonary exercise ergometer and MedBIKE™ (1.1 ± 0.5 L/minute versus 1.1 ± 0.5 L/minute, p = 0.44). Ten youth with Fontan physiology (11.5 ± 1.8 years old) completed a MedBIKE™ high-intensity interval training session with no adverse events. The participants found the MedBIKE™ to be enjoyable and easy to navigate. In two participants, the 8-week home-based protocol was tolerated well with completion of 23/24 (96%) and 24/24 (100%) of sessions, respectively, and no adverse events across the 47 sessions in total. CONCLUSION: The MedBIKE™ resulted in similar physiological responses as compared to a cardiopulmonary exercise test ergometer and the high-intensity interval training protocol was safe, feasible, and enjoyable in youth with Fontan physiology. A randomised-controlled trial of a home-based high-intensity interval training exercise intervention using the MedBIKE™ will next be undertaken.

Rupture of Abdominal Aortic Aneurysm in Patients with and without Antecedent Endovascular Repair.

BACKGROUND: Reported results of ruptured abdominal aortic aneurysm (rAAA) in patients with antecedent endovascular aneurysm repair (EVAR) to those presenting with de novo rupture show a similar or slightly improved outcome. The aim of this study was to compare differences in the presentation and outcomes of rAAA with and without prior EVAR. METHODS: A retrospective review of 121 patients with rAAA, ruptured identified 2 groups. Group A included 17 patients (rAAA n = 17) with antecedent EVAR and group B consisted of 104 patients (rAAA n = 104) with de novo ruptures, from January 2001 to March 2015 in 3 teaching hospitals. Patient characteristics and perioperative variables were compared; Fisher's exact test was used for categorical variables. For continuous variables, Student's t-test and Mann-Whitney U test were used. RESULTS: Both groups were similar in age, gender, the incidence of hypertension, coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease, and nicotine abuse. Mean time of presentation from EVAR to rupture in group A was 42 ± 22 months. Mean preoperative transverse or anteroposterior diameter of AAA was 6.6 cm in group A and 7.1 cm in group B. Three patients of 17 (17.6%) in group A were hemodynamically unstable as compared to 47 of 104 patients (45.1%) in group B (P = 0.03). Mean red blood cells, fresh frozen plasma, and platelet transfusion were similar in both groups. Thirty-day mortality was 8 of 17 (44.7%) in group A and 44 of 104 (42.3%) in group B (P = 1.0). Postoperative complications were also similar in both groups except the incidence of postoperative respiratory failure was higher in group B (38%) as compared with 11.1% in group A (P = 0.001). CONCLUSIONS: Patients presenting with rAAA with antecedent EVAR are hemodynamically more stable as compared with patients with de novo rupture of AAA. Postoperative respiratory failure is more common in patients with de novo rupture. rAAA carry high mortality with and without prior EVAR.

Reported electronic cigarette use among adolescents in the Niagara region of Ontario.

BACKGROUND: Use of electronic cigarettes (e-cigarettes) among adolescents has not been fully described, in particular their motivations for using them and factors associated with use. We sought to evaluate the frequency, motivations and associated factors for e-cigarette use among adolescents in Ontario. METHODS: We conducted a cross-sectional study in the Niagara region of Ontario, Canada, involving universal screening of students enrolled in grade 9 in co-operation with the Heart Niagara Inc. Healthy Heart Schools' Program (for the 2013-2014 school year). We used a questionnaire to assess cigarette, e-cigarette and other tobacco use, and self-rated health and stress. We assessed household income using 2011 Canadian census data by matching postal codes to census code. RESULTS: Of 3312 respondents, 2367 answered at least 1 question in the smoking section of the questionnaire (1274 of the 2367 respondents [53.8%] were male, with a mean [SD] age of 14.6 [0.5] yr) and 2292 answered the question about use of e-cigarettes. Most respondents to the questions about use of e-cigarettes (n = 1599, 69.8%) had heard of e-cigarettes, and 380 (23.8%) of these respondents had learned about them from a store sign or display. Use of e-cigarettes was reported by 238 (10.4%) students. Most of the respondents who reported using e-cigarettes (171, 71.9%) tried them because it was "cool/fun/new," whereas 14 (5.8%) reported using them for smoking reduction or cessation. Male sex, recent cigarette or other tobacco use, family members who smoke and friends who smoke were strongly associated with reported e-cigarette use. Reported use of e-cigarettes was associated with self-identified fair/poor health rating (odds ratio [OR] 1.9 (95% confidence interval [CI] 1.2-3.0), p < 0.001), high stress level (OR 1.7 (95% CI 1.1-2.7), p < 0.001) and lower mean (33.4 [8.4] × $1000 v. 36.1 [10.7] × $1000, p = 0.001) and median [interquartile range] (26.2 [5.6] × $1000 v. 28.1 [5.7] × $1000) household incomes. INTERPRETATION: Use of e-cigarettes is common among adolescents in the Niagara region and is associated with sociodemographic features. Engaging in seemingly exciting new behaviours appears to be a key motivating factor rather than smoking cessation.

Universal screening for cardiovascular disease risk factors in adolescents to identify high-risk families: a population-based cross-sectional study.

BACKGROUND: Universal screening of children for dyslipidemia and other cardiovascular risk factors has been recommended. Given the clustering of cardiovascular risk factors within families, one benefit of screening adolescents may be to identify "at-risk" families in which adult members might also be at elevated risk and potentially benefit from medical evaluation. METHODS: Cross-sectional study of grade 9 students evaluating adiposity, lipids and blood pressure. Data collected by Heart Niagara Inc. through the Healthy Heart Schools' Program. Parents completed questionnaires, evaluating family history of dyslipidemia, hypertension, diabetes and early cardiovascular disease events in parents and siblings (first-degree relatives), and grandparents (second-degree relatives). Associations between positive risk factor findings in adolescents and presence of a positive family history were assessed in logistic regression models. RESULTS: N = 4014 adolescents ages 14-15 years were screened; 3467 (86 %) provided family medical history. Amongst adolescents, 4.7 % had dyslipidemia, 9.5 % had obesity, and 3.5 % had elevated blood pressure. Central adiposity (waist-to-height ratio ≥0.5) in the adolescent was associated with increased odds of diabetes in first- (OR:2.0 (1.6-2.6), p < 0.001) and second-degree relatives (OR:1.3 (1.1-1.6), p = 0.002). Dyslipidemia was associated with increased odds of diabetes (OR:1.6 (1.1-2.3), p < 0.001), hypertension (OR:2.2 (1.5-3.2), p < 0.001) and dyslipidemia (OR:2.2 (1.5-3.2),p < 0.001) in first degree relatives. Elevated blood pressure did not identify increased odds of a positive family history. CONCLUSIONS: Presence of obesity and/or dyslipidemia in adolescents identified through a universal school-based screening program is associated with risk factor clustering within families. Universal pediatric cardiometabolic screening may be an effective entry into reverse cascade screening.

Hyperintense cortical signal on magnetic resonance imaging reflects focal leukocortical encephalitis and seizure risk in progressive multifocal leukoencephalopathy.

OBJECTIVE: To determine the frequency of hyperintense cortical signal (HCS) on T1-weighted precontrast magnetic resonance (MR) images in progressive multifocal leukoencephalopathy (PML) patients, its association with seizure risk and immune reconstitution inflammatory syndrome (IRIS), and its pathologic correlate. METHODS: We reviewed clinical data including seizure history, presence of IRIS, and MR imaging scans from PML patients evaluated at our institution between 2003 and 2012. Cases that were diagnosed either using cerebrospinal fluid JC virus (JCV) polymerase chain reaction, brain biopsy, or autopsy, and who had MR images available were included in the analysis (n=49). We characterized pathologic findings in areas of the brain that displayed HCS in 2 patients and compared them with isointense cortex in the same individuals. RESULTS: Of 49 patients, 17 (34.7%) had seizures and 30 (61.2%) had HCS adjacent to subcortical PML lesions on MR images. Of the 17 PML patients with seizures, 15 (88.2%) had HCS compared with 15 of 32 (46.9%) patients without seizures (p=0.006). HCS was associated with seizure development with a relative risk of 4.75 (95% confidence interval=1.2-18.5, p=0.006). Of the 20 patients with IRIS, 16 (80.0%) had HCS compared with 14 of 29 (49.3%) patients without IRIS (p=0.04). On histological examination, HCS areas were associated with striking JCV-associated demyelination of cortical and subcortical U fibers, significant macrophage infiltration, and a pronounced reactive gliosis in the deep cortical layers. INTERPRETATION: Seizures are a frequent complication in PML. HCS is associated with seizures and IRIS, and correlates histologically with JCV focal leukocortical encephalitis.