Congenital aneurysm of sinus of valsalva ruptured into right ventricle diagnosed by magnetic resonance imaging.

Rupture of a congenital aneurysm of the sinus of Valsalva is a rare congenital cardiac malformation. This case report describes a congenital aneurysm of the sinus of Valsalva which ruptured into the right ventricle in a 3-year-old girl. The exact route of the fistula through the cardiac walls and the localization of the rupture into the right ventricle was not completely defined by two-dimensional and color Doppler echocardiography and could be determined only by magnetic resonance imaging (MRI).

Proposal of a new classification for optimising outcome assessment following partial cricotracheal resections in severe pediatric subglottic stenosis.

OBJECTIVE: Creation of a patent subglottic airway after partial cricotracheal resection (PCTR) may not always result in successful decannulation due to associated parameters such as co-morbidity and/or glottic involvement. We classified patients after incorporating these additional parameters into the original Myer-Cotton classification to assess whether this could better predict the outcome measures after PCTR. METHODS: One hundred children with Myer-Cotton grade III or IV subglottic stenosis who underwent PCTR between 1978 and 2008 were identified from a prospectively collected database. The patients were classified into four groups based on the association of co-morbidity and/or glottic involvement. Delay in decannulation, revision open surgery and rates of decannulation were the outcome measures compared between the groups. RESULTS: There were 68 children with Myer-Cotton grade III and 32 children with grade IV stenosis. Based on the new classification, there were 36 children with isolated SGS, 31 with associated co-morbidity, 19 with associated glottic involvement and 14 children with both co-morbidity and glottic involvement. A trend towards less optimal results was noticed with the association of co-morbidity and/or glottic involvement. Statistical significance was reached for maximum decannulation failure in the group with both co-morbidity and glottic involvement. Delayed decannulation significantly correlated in the group with associated glottic involvement. CONCLUSION: This new classification is relatively simple and aimed at providing more accurate and uniform prognostic information to both patients and surgeons when dealing with the whole spectrum of severe SGS.

Atherosclerotic renal artery stenosis: update on management strategies.

Purpose of reviewAtherosclerotic renal artery stenosis (ARAS) usually occurs in patients at high risk of vascular disease, and is associated with increased mortality. The primary goals of ARAS treatment include the control of blood pressure (BP), the improved renal function, and the benefit on cardiovascular events. Although medical therapy remains the standard approach to the management of ARAS, percutaneous transluminal renal angioplasty (PTRA) revascularization can be a therapeutic option under certain conditions.Recent findingsRecent evidence confirms that ARAS increases cardiovascular risk, independent of BP and renal function. This suggests that revascularization might potentially improve overall prognosis, but no data are available currently. In cases of significant ARAS, the accepted indications for PTRA are uncontrollable hypertension, gradual or acute renal function decline with the use of agents blocking the renin-angiotensin-aldosterone system, and recurrent flash pulmonary edema. The key point of treatment success remains in all cases a careful patient selection.SummaryAlthough the atherosclerotic lesions of the renal arteries tend to progress over time, the anatomical lesion progression is not always associated with changes in BP. Furthermore, a poor correlation was noted between the degree of anatomic stenosis and glomerular filtration rate. The high cardiovascular risk warrants aggressive pharmacological treatment to prevent progression of the generalized vascular disorder. Ongoing trials will show whether PTRA revascularization has added, long-term effects on BP, renal function, and cardiovascular prognosis. With or without PTRA revascularization, medical therapy using antihypertensive agents, statins, and aspirin is necessary in almost all cases.

Traumatic mitral valve injury after blunt chest trauma: a case report and review of the literature.

Mitral valve injury after blunt chest trauma is a rare occurrence. We recently admitted a patient with severe traumatic mitral regurgitation who was successfully treated with surgery. Review of the literature aimed at taking an inventory of cases of traumatic nonpenetrating mitral insufficiency that were operated on, since the earliest report in 1964. Eighty-two cases were found and analyzed allowing for a better understanding of the epidemiology, etiology, natural history, pathology, and treatment of this rare condition. The most common lesions reach the papillary muscles (PM), followed by the chordae and then the mitral valve leaflets. Among the 82 cases reported that have been treated with surgery, 57% required a valve replacement. More than half of the patients had a PM injury with a complete or partial rupture. When the rupture is complete, and especially when it involves the anterior PM, the clinical picture is most always acute with clinically important hemodynamic repercussions, often necessitating emergency surgery, most of the time with mitral valve replacement. One must always suspect traumatic mitral injury after blunt chest trauma. The most common mitral lesions affect the PM. The clinical course can be indolent or devastating, and most often requires urgent or delayed surgical treatment, either with mitral valve repair or replacement.

Congenital hydrocephalus--prevalence, prenatal diagnosis and outcome of pregnancy in four European regions.

OBJECTIVE: To describe prevalence, prenatal diagnosis and outcome for fetuses and infants with congenital hydrocephalus. METHODS: Data were taken from four European registries of congenital malformations (EUROCAT). The registries included are based on multiple sources of information and include information about livebirths, fetal deaths with GA > or = 20 weeks and terminations of pregnancy for fetal anomaly (TOPFA). All cases from the four registries diagnosed with congenital hydrocephalus and born in the period 1996-2003 were included in the study. Cases with hydrocephalus associated with neural tube defects were not included in the study. RESULTS: Eighty-seven cases with congenital hydrocephalus were identified during the study period giving an overall prevalence of 4.65 per 10,000 births. There were 41 livebirths (47%), four fetal deaths (5%) and 42 TOPFA (48%). Nine percent of all cases were from a multiple pregnancy. Additional non-cerebral major malformations were diagnosed in 38 cases (44%) and karyotype anomalies in eight cases (9%). Median GA at TOPFA was 21 weeks. Among livebirths 61% were diagnosed prenatally at a median GA of 31 weeks (range 17-40 weeks) and median GA at birth was 37 weeks. Fourteen liveborn infants (34%) died within the first year of life with the majority of deaths during the first week after birth. CONCLUSION: Congenital hydrocephalus is a severe congenital malformation often associated with other congenital anomalies. CH is often diagnosed prenatally, although sometimes late in pregnancy. A high proportion of affected pregnancies result in termination for severe fetal anomaly and there is a high mortality in livebirths.

Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma.

Giant congenital naevi are pigmented childhood lesions that frequently lead to melanoma, the most aggressive skin cancer. The mechanisms underlying this malignancy are largely unknown, and there are no effective therapies. Here we describe a mouse model for giant congenital naevi and show that naevi and melanoma prominently express Sox10, a transcription factor crucial for the formation of melanocytes from the neural crest. Strikingly, Sox10 haploinsufficiency counteracts Nras(Q61K)-driven congenital naevus and melanoma formation without affecting the physiological functions of neural crest derivatives in the skin. Moreover, Sox10 is also crucial for the maintenance of neoplastic cells in vivo. In human patients, virtually all congenital naevi and melanomas are SOX10 positive. Furthermore, SOX10 silencing in human melanoma cells suppresses neural crest stem cell properties, counteracts proliferation and cell survival, and completely abolishes in vivo tumour formation. Thus, SOX10 represents a promising target for the treatment of congenital naevi and melanoma in human patients.

Reversible acquired epileptic frontal syndrome and CSWS suppression in a child with congenital hemiparesis treated by hemispherotomy

Rapport de synthèse : Cette thèse a étudié en détail le cas d'un enfant souffrant d'une hémiplégie congénitale sur un infarctus prénatal étendu qui a développé une forme particulière d'épilepsie, le syndrome des pointes ondes continues du sommeil (POCS), associé à une régression mentale massive. Les caractéristiques de cette détérioration pointaient vers un dysfonctionnement de type frontal. Une chirurgie de l'épilepsie (hémisphérotomie) a, non seulement, permis la guérison de l'épilepsie mais une récupération rapide sur le plan comportemental et cognitif, suivie d'une reprise plus lente du développement, avec finalement à l'âge de 11 ans un niveau de déficience intellectuelle modérée. L'intérêt de cette étude réside dans le fait que l'enfant a pu être suivi prospectivement entre l'âge de 4.5 ans et 11 ans par des enregistrements électro-encéphalographiques (EEG) ainsi que des tests neuropsychologiques et des questionnaires de comportements sériés, permettant de comparer les périodes pré-, péri- et postopératoires, ce qui est rarement réalisable. Un enregistrement EEG de surface a même pu être effectué durant l'opération sur l'hémisphère non lésé, permettant de documenter l'arrêt des décharges épileptiformes généralisées dès la fin de l'intervention. L'hypothèse que nous avons- souhaité démontrer est que la régression comportementale et cognitive présentée par l'enfant après une période de développement précoce presque normale (retard de langage) était de nature épileptique : nous l'expliquons par la propagation de l'activité électrique anormale à partir de la lésion de l'hémisphère gauche vers les régions préservées, en particulier frontales bilatérales. L'hémisphérotomie a permis une récupération rapide en déconnectant l'hémisphère gauche lésé et épileptogène de l'hémisphère sain, qui a ainsi pu reprendre les fonctions cognitives les plus importantes. Les progrès plus lents par la suite et l'absence de rattrapage au delà d'un niveau de déficience mentale modérée sont plus difficiles à expliquer: on postule ici un effet de l'épilepsie sur le développement de réseaux neuronaux de l'hémisphère initialement non lésé, réseaux qui sont à la fois à un stade précoce de leur maturation et en cours de réorganisation suite à la lésion prénatale. La littérature sur les déficits cognitifs avant et après hemisphérotomie s'est surtout préoccupée du langage et de sa récupération possible. À notre connaissance, notre étude est la première à documenter la réversibilité d'une détérioration mentale avec les caractéristiques d'un syndrome frontal après hémisphérotomie. La chirurgie de l'épilepsie a offert ici une occasion unique de documenter le rôle de l'activité épileptique dans la régression cognitive puisqu'en interrompant brusquement la propagation de l'activité électrique anormale, on a pu comparer la dynamique du développement avant et après l'intervention. La mise en relation des multiples examens cliniques et EEG pratiqués chez un seul enfant sur plusieurs années a permis d'obtenir des informations importantes dans la compréhension des troubles cognitifs et du comportement associés aux épilepsies focales réfractaires. ABSTRACT : A boy with a right congenital hemiparesis due to a left pre-natal middle cerebral artery infarct developed focal epilepsy at 33 months and then an insidious and subsequently more rapid, massive cognitive and behavioural regression with a frontal syndrome between the ages of 4 and 5 years with continuous spike-waves during sleep (CSWS) on the EEG. Both the epilepsy and the CSWS were immediately suppressed by hemispherotomy at the age of 5 years and 4months. A behavioural-cognitive follow-up prior to hemispheratomy, an per-operative EEG and corticography and serial post-operative neuropsychological assessments were performed until the age of 11 years. The spread of the epileptic activity to the "healthy" frontal region was the cause of the reversible frontal syndrome. A later gradual long-term but incomplete cognitive recovery, with moderate mental disability was documented. T9ris outcome is probably explained by another facet of the epilepsy, namely the structural effects of prolonged epileptic dischazges in rapidly developing cerebral networks which are, at the same time undergoing the reorganization imposed by a unilateral early hemispheric lesion. Group studies on the outcome of children before and after hemispherectomy using only single IQ measures, pre- and postoperatively, may miss particular epileptic cognitive dysfunctions as they are likely to be different from case to case. Such detailed and rarely available complementary clinical and EEG data obtained in a single case at different time periods in relation to the epilepsy, including peroperative electrophysiological findings, may help to understand the different cognitive deficits and recovery profiles and the limits of full cognitive recovery.

Isolated congenital atrioventricular block diagnosed in utero: natural history and outcome.

BACKGROUND: Isolated congenital atrioventricular block (CAVB) diagnosed in utero is associated with a high morbidity and mortality. Prognosis is especially poor when heart rate drops below 55 beats per minute (bpm) and when fetal hydrops develops. We describe the natural history and outcome of 24 infants with isolated CAVB diagnosed in utero, review the literature, and assess the risk factors that could predict outcome. METHODS: This was a retrospective multicenter study of 24 patients with isolated CAVB diagnosed in utero. RESULTS: CAVB was detected at a mean gestational age (GA) of 24.7 +/- 5.1 weeks. Ten fetuses initially presented with complete heart block. Low heart rate or incomplete heart block was the first documentation of bradyarrhythmia in the other 14 fetuses. In 11 of them, CAVB developed during pregnancy after a median time of 3 (range 1-16) weeks. Fetal hydrops developed in 10 of 24 (42%) fetuses at a mean GA of 27.6 +/- 5.1 weeks. Hydropic fetuses showed lower heart rates during pregnancy (47 +/- 10 bpm) than non-hydropic fetuses (57 +/- 10 bpm). There were three intrauterine deaths; all were hydropic and female. Nine viable females and 12 males were born at a mean GA of 37.1 +/- 6.1 weeks with an average birth weight of 3097 +/- 852 g. Fifteen CAVB patients required pacemaker (PM) intervention, 10 of them immediately after birth. Dilated cardiomyopathy (DCM) developed in three infants of whom two died of congestive heart failure, shortly after the diagnosis was made; one is still alive. Mortality before or after birth was 21%, and was associated with heart rates below 50 bpm and development of fetal hydrops. Poor outcome, defined as death, PM implantation, or development of DCM, occurred in 83% of cases and was associated with heart rates below 60 bpm during pregnancy. CONCLUSIONS: Isolated CAVB diagnosed in utero is associated with high morbidity and mortality. Patients who develop fetal hydrops show lower heart rates during pregnancy than patients who do not. A fetal heart rate below 50 bpm and development of fetal hydrops is associated with increased mortality. Rates below 60 bpm are associated with PM requirement and/or DCM.

Myxoma on a mechanical mitral valve annulus.

To date, myxoma on a mechanical valve annulus has not been reported. The case is reported of a 74-year-old woman who was admitted to hospital following the identification of an intracardiac tumor mass. Six years previously, the patient had received a mechanical valve implanted in the mitral position. Transesophageal echocardiography revealed a mobile hypoechogenic tumorous mass attached to the anterior annulus of the prosthesis. The tumor was successfully treated by surgical excision, and a diagnosis of myxoma was confirmed both clinically and pathologically.

Respiratory self-navigated postcontrast whole-heart coronary MR angiography: initial experience in patients.

PURPOSE: To assess the diagnostic performance of respiratory self-navigation for whole-heart coronary magnetic resonance (MR) angiography in a patient cohort referred for diagnostic cardiac MR imaging. MATERIALS AND METHODS: Written informed consent was obtained from all participants for this institutional review board-approved study. Self-navigated coronary MR angiography was performed after administration of a contrast agent in 78 patients (mean age, 48.5 years ± 20.7 [standard deviation]; 53 male patients) referred for cardiac MR imaging because of coronary artery disease (n = 40), cardiomyopathy (n = 14), congenital anomaly (n = 17), or "other" (n = 7). Examination duration was recorded, and the image quality for each coronary segment was assessed with consensus reading. Vessel sharpness, length, and diameter were measured. Quantitative values in proximal, middle, and distal segments were compared by using analysis of variance and t tests. A double-blinded comparison with the results of x-ray angiography was performed when such results were available. RESULTS: When patients with different indications for cardiac MR imaging were examined with self-navigated postcontrast coronary MR angiography, whole-heart data sets with 1.15-mm isotropic spatial resolution were acquired in an average of 7.38 minutes ± 1.85. The main and proximal coronary segments could be visualized in 92.3% of cases, while the middle and distal segments could be visualized in 84.0% and 55.8% of cases, respectively. Subjective scores and vessel sharpness were significantly higher in the proximal segments than in the middle and distal segments (P < .05). Anomalies of the coronary arteries could be confirmed or excluded in all cases. Per-vessel sensitivity and specificity for stenosis detection were 64.7% and 85.0%, respectively, in the 31 patients for whom reference standard x-ray coronary angiography results were available. CONCLUSION: The self-navigated coronary MR angiography sequence shows promise for coronary imaging. However, technical improvements are needed to improve image quality, especially in the more distal coronary segments.

Altered expression of beta-galactosidase-1-like protein 3 (Glb1l3) in the retinal pigment epithelium (RPE)-specific 65-kDa protein knockout mouse model of Leber's congenital amaurosis

Purpose: In this study, we investigated the expression of the gene encoding beta-galactosidase (Glb)-1-like protein 3 (Glb1l3), a member of the glycosyl hydrolase 35 family, during retinal degeneration in the retinal pigment epithelium (RPE)-specific 65-kDa protein knockout (Rpe65(-/-)) mouse model of Leber congenital amaurosis (LCA). Additionally, we assessed the expression of the other members of this protein family, including beta-galactosidase-1 (Glb1), beta-galactosidase-1-like (Glb1l), and beta-galactosidase-1-like protein 2 (Glb1l2).Methods: The structural features of Glb1l3 were assessed using bioinformatic tools. mRNA expression of Glb-related genes was investigated by oligonucleotide microarray, real-time PCR, and reverse transcription (RT) -PCR. The localized expression of Glb1l3 was assessed by combined in situ hybridization and immunohistochemistry.Results: Glb1l3 was the only Glb-related member strongly downregulated in Rpe65(-/-) retinas before the onset and during progression of the disease. Glb1l3 mRNA was only expressed in the retinal layers and the RPE/choroid. The other Glb-related genes were ubiquitously expressed in different ocular tissues, including the cornea and lens. In the healthy retina, expression of Glb1l3 was strongly induced during postnatal retinal development; age-related increased expression persisted during adulthood and aging.Conclusions: These data highlight early-onset downregulation of Glb1l3 in Rpe65-related disease. They further indicate that impaired expression of Glb1l3 is mostly due to the absence of the chromophore 11-cis retinal, suggesting that Rpe65 deficiency may have many metabolic consequences in the underlying neuroretina.

An unexpected role of semaphorin3a-neuropilin-1 signaling in lymphatic vessel maturation and valve formation.

RATIONALE: Lymphatic vasculature plays important roles in tissue fluid homeostasis maintenance and in the pathology of human diseases. Yet, the molecular mechanisms that control lymphatic vessel maturation remain largely unknown. OBJECTIVE: We analyzed the gene expression profiles of ex vivo isolated lymphatic endothelial cells to identify novel lymphatic vessel expressed genes and we investigated the role of semaphorin 3A (Sema3A) and neuropilin-1 (Nrp-1) in lymphatic vessel maturation and function. METHODS AND RESULTS: Lymphatic and blood vascular endothelial cells from mouse intestine were isolated using fluorescence-activated cell sorting, and transcriptional profiling was performed. We found that the axonal guidance molecules Sema3A and Sema3D were highly expressed by lymphatic vessels. Importantly, we found that the semaphorin receptor Nrp-1 is expressed on the perivascular cells of the collecting lymphatic vessels. Treatment of mice in utero (E12.5-E16.5) with an antibody that blocks Sema3A binding to Nrp-1 but not with an antibody that blocks VEGF-A binding to Nrp-1 resulted in a complex phenotype of impaired lymphatic vessel function, enhanced perivascular cell coverage, and abnormal lymphatic vessel and valve morphology. CONCLUSIONS: Together, these results reveal an unanticipated role of Sema3A-Nrp-1 signaling in the maturation of the lymphatic vascular network likely via regulating the perivascular cell coverage of the vessels thus affecting lymphatic vessel function and lymphatic valve development.

Trial of recombinant follicle-stimulating hormone pretreatment for gnrh-induced fertility in patients with congenital hypogonadotropic hypogonadism.

CONTEXT AND OBJECTIVE: The optimal strategy for inducing fertility in men with congenital hypogonadotropic hypogonadism (CHH) is equivocal. Albeit a biologically plausible approach, pretreatment with recombinant FSH (rFSH) before GnRH/human chorionic gonadotropin administration has not been sufficiently assessed. The objective of the study was to test this method. DESIGN AND SETTING: This was a randomized, open-label treatment protocol at an academic medical center. PATIENTS AND INTERVENTIONS: GnRH-deficient men (CHH) with prepubertal testes (<4 mL), no cryptorchidism, and no prior gonadotropin therapy were randomly assigned to either 24 months of pulsatile GnRH therapy alone (inducing endogenous LH and FSH release) or 4 months of rFSH pretreatment followed by 24 months of GnRH therapy. Patients underwent serial testicular biopsies, ultrasound assessments of testicular volume, serum hormone measurements, and seminal fluid analyses. RESULTS: rFSH treatment increased inhibin B levels into the normal range (from 29 ± 9 to 107 ± 41 pg/mL, P < .05) and doubled testicular volume (from 1.1 ± 0.2 to 2.2 ± 0.3 mL, P < .005). Histological analysis showed proliferation of both Sertoli cells (SCs) and spermatogonia, a decreased SC to germ cell ratio (from 0.74 to 0.35), and SC cytoskeletal rearrangements. With pulsatile GnRH, the groups had similar hormonal responses and exhibited significant testicular growth. All men receiving rFSH pretreatment developed sperm in their ejaculate (7 of 7 vs 4 of 6 in the GnRH-only group) and showed trends toward higher maximal sperm counts. CONCLUSIONS: rFSH pretreatment followed by GnRH is successful in inducing testicular growth and fertility in men with CHH with prepubertal testes. rFSH not only appears to maximize the SC population but also induces morphologic changes, suggesting broader developmental roles.

Integrating postoperative value of cardiac Troponin I for a better correlation with in-hospital outcomes after congenital heart surgery.

Objective: Cardiac Troponin-I (cTnI) is a well-recognized early postoperative marker for myocardial damage in adults and children after heart surgery. The present study was undertaken to evaluate whether the integrated value (area under the curve(AUC)) of postoperative cTnI is a better mode to predict long-term outcome than post operative cTnI maximum value, after surgery for congenital heart defects (CHD). Methods: retrospective cohort study. 279 patients (mean age 4.6 years; range 0-17 years-old, 185 males) with congenital heart defect repair on cardiopulmonary by-pass were retrieved from our database including postoperative cTnI values. Maximal post operative cTnI value, post operative cTnI AUC value at 48h and total post operative cTnI AUC value were calculated and then correlated with duration of intubation, duration of ICU stay and mortality. Results: the mean duration of mechanical ventilation was 5.1+/-7.2 days and mean duration of ICU stay was 11.0+/- 13.3 days,11 patients (3.9%) died in post operative period. When comparing survivor and deceased groups, there was a significant difference in the mean value for max cTnI (16.7+/- 21.8 vs 59.2+/-41.4 mcg/l, p+0.0001), 48h AUC cTnI (82.0+/-110.7 vs 268.8+/-497.7 mcg/l, p+0.0001) and total AUC cTnI (623.8+/-1216.7 vs 2564+/-2826.0, p+0.0001). Analyses for duration of mechanical ventilation and duration of ICU stay by linear regression demonstrated a better correlation for 48h AUC cTnI (ventilation time r+0.82, p+0.0001 and ICU stay r+0.74, p+0.0001) then total AUC cTnI (ventilation time r+0.65, p+0.0001 and ICU stay r+0.60, p+0.0001) and max cTnI (ventilation time r+0.64, p+0.0001 and ICU stay r+0.60, p+0.0001). Conclusion: Cardiac Troponin I is a specific and sensitive marker of myocardial injury after congenital heart surgery and it may predict early in-hospital outcomes. Integration of post operative value of cTnI by calculation of AUC improves prediction of early in-hospital outcomes. It probably takes into account, not only the initial surgical procedure, but probably also incorporates the occurrence of hypoxic-ischemic phenomena in the post-operative period.