Evolution of Extracranial Internal Carotid Artery Disease in Children With Sickle Cell Anemia.

BACKGROUND: Cerebral arteriopathy in patients with sickle cell anemia mainly affects the intracranial anterior circulation. However, the extracranial internal carotid artery (eICA) can also be stenosed and responsible for ischemic lesions. In children with sickle cell anemia, we perform routine annual Doppler ultrasound assessment of the eICA and magnetic resonance imaging with 3-dimensional time-of-flight magnetic resonance angiography of the Willis circle and neck arteries in those with abnormal velocity. Our aim was to report the evolution of eICA stenoses from 2011 to the present as a function of therapy in a retrospective case-series study. We hypothesized that chronic transfusion (CTT) would be more effective than hydroxyurea and simple observation on the evolution of eICA stenosis. METHODS: Eligibility criteria were a history of eICA velocity ≥160 cm/s with a minimum Doppler and magnetic resonance imaging follow-up of 1 year. eICAs were graded for stenosis according to NASCET (The North American Symptomatic Carotid Endarterectomy Trial). Magnetic resonance imaging was investigated for ischemic lesions. Treatment with hydroxyurea and CTT were obtained from the chart review. RESULTS: Fifty-four patients were included. Eight patients had a stroke history. The median (range) follow-up was 4.7 years (1.1-9.2 years). On the first neck magnetic resonance angiography, stenosis was present in 48/54 (89%) patients. Kinking was found in 39/54 (72%) patients. On the last neck magnetic resonance angiography, the proportion of patients with eICA stenosis decreased to 39/54 (72%). ICA occlusion occurred in 5 patients despite CTT. Three patients had carotid webs without intracranial stenosis. The proportion of patients with improvement in stenosis score was 8% with no treatment intensification, 20% with hydroxyurea, and 48% with CTT (P=0.016). The mean (SD) change per year in stenosis score was 0.40 (0.60) without intensification, 0.20 (0.53) with hydroxyurea, and -0.18 (0.55) with CTT (P=0.006). Ischemic lesions were present initially in 46% of patients, and the incidence of progressive ischemic lesions was 2.5 events/100 patient-years. Cox regression analysis showed that the initial score for eICA stenosis was a significant predictive factor for the risk of new silent cerebral infarct events. CONCLUSIONS: Our study reinforces the need to assess cervical arteries for better prevention of cerebral ischemia and encourage initiation of CTT in sickle cell anemia children with eICA stenosis.

Predictors of cochleovestibular dysfunction in children with congenital cytomegalovirus infection.

The purpose of this study is to assess the predictive factors of both hearing and vestibular impairment in congenitally cytomegalovirus-infected children (cCMV) through a multivariate analysis of clinical and imaging characteristics collected during pregnancy and at birth. This retrospective study was conducted between March 2014 and March 2020, including confirmed congenitally CMV-infected children with a complete vestibular and hearing assessment. Data concerning pregnancy, date of infection, clinical characteristics, and symptomatology at birth were collected. In total, 130 children were included, with a median age of 21 months. Eighty-three children (64%) presented with an inner ear impairment (both cochlear and vestibular impairment). Sex, modality of maternal infection (seroconversion or reactivation), pregnancy term, weight and head circumference at birth, neonatal clinical signs of infection, and treatment were not significantly correlated with inner ear impairment. However, multivariate analysis confirmed that there are two independent predictive factors of inner ear impairment: antenatal imaging lesions (ORa = 8.02 [1.74; 60.27], p-value = 0.01) and infection during the first trimester (ORa = 4.47 [1.21; 19.22], p-value = 0.03). Conversely, infections occurring during the second trimester were rarely associated with inner ear impairment: 4/13 (31%) in our series, with vestibular impairment alone (4/4) and no hearing loss. None of the children infected during the third trimester developed inner ear dysfunction. CONCLUSION: Besides the symptomatic status of the CMV infection at birth, we found that antenatal imaging brain damage and early infection (mainly during the first trimester) constitute the two best independent predictive factors of inner ear involvement in congenitally CMV-infected children. WHAT IS KNOWN: • Congenital cytomegalovirus infection is the leading infectious cause of neurological disabilities and sensorineural hearing loss in children and responsible of vestibular disorders, which are probably underestimated. • No articles have yet defined the predictive factors of the entire inner ear impairment (vestibule and cochlea). WHAT IS NEW: • The timing of the infection during pregnancy (first and second trimester, ORa=4.47) and antenatal imaging lesions (ORa=8.02) are independently predictive (in a multivariate analysis) of inner ear involvement. • The symptomatic status at birth is a poor predictor of inner ear impairment.

[Pulmonary glial heterotopia: Unique lesion in an infant with anencephalic twin]. / Hétérotopie gliale pulmonaire : une lésion exceptionnelle chez un nourrisson avec un jumeau anencéphale.

Pulmonary glial heterotopia is an extremely rare entity whose pathophysiology remains unclear. We report for the first time one case of pulmonary glial heterotopia occured in a one-month baby free from any malformation. She has the particularity of being born from monozygotic monochorionic twin pregnancy where her anencephalic exencephalic sister suffered a medical termination of pregnancy. She presented neonatal respiratory distress, which recurred one month later. Chest X-ray revealed bilateral cystic pulmonary lesions mainly located in the right lung. Given the suspicion of congenital cystic adenomatoid malformation (CCAM), she underwent an upper and a lower right lung lobectomy at four months old. The pathological study found a multi-cystic lesion consisted of well-differentiated and poorly cellular glial tissue sometimes lined by bronchic epithelium. There was no pathological evidence for a CCAM. The evolution was favorable after surgery with an infant who was well five months later. This is one of the very few cases where the disease did not lead to rapid death in utero or during the perinatal period. This suggests that effective management by surgery could be a decisive factor in the survival of these patients.

Posterior urethral valves and vesicoureteral reflux: can prenatal ultrasonography distinguish between these two conditions in male fetuses?

OBJECTIVE: The objective of the study was to evaluate prenatal sonographic signs that distinguish male fetuses with posterior urethral valves (PUV) from those with vesicoureteral reflux (VUR). METHODS: Prenatal data were retrospectively retrieved from all consecutive women delivering between 2003 and 2012 of a male newborn with a postnatal diagnosis of PUV or VUR. Prenatal parameters included fetal bladder characteristics, identification of a dilated posterior urethra, and change in shape and size in the fetal renal pelvis or ureter. RESULTS: One hundred thirty-six women gave birth to a male newborn with a postnatal diagnosis of PUV (n = 49) or VUR (n = 87). The presence of posterior urethral dilatation [21 (42.9%) fetuses versus 0 (0%), p = 0.000], a thickened fetal bladder wall [37 (75.5%) vs 4 (4.6%), p = 0.000], and anhydramnios [14 (28.6%) vs 0, p = 0.000] were strongly associated with the postnatal diagnosis of PUV. Change in shape and size in the fetal renal pelvis or ureter was observed in 15 (17.2%) of 87 children with VUR versus 1 (2.0%) out of 49 with PUV (p = 0.010). CONCLUSIONS: Prenatal ultrasound may differentiate with reasonable accuracy male fetuses with a postnatal diagnosis of PUV from those with VUR. © 2016 John Wiley & Sons, Ltd.

Plummer-Vinson Syndrome in Children.

OBJECTIVES: Plummer-Vinson syndrome (PVS), also called Kelly-Paterson syndrome, is a rare cause of dysphagia in children. This syndrome associates single or multiple webs in the upper esophagus with frequent iron deficiency. METHODS: We reported 3 pediatric cases of PVS before analyzing all of the cases of PVS in children reported in the PubMed and EMBASE databases. RESULTS: Among 17 reported PVS cases in children, all of the patients experienced iron-deficiency anemia, and no immunological disease was reported. The male/female ratio was 1/1.9, and most cases were observed in adolescents. Conversely to adults, endoscopic dilation was often necessary because dysphagia resisted iron supplementation. A single dilation was usually sufficient. One case of pediatric PVS experienced esophageal cancer in adulthood. CONCLUSIONS: In the case of dysphagia in children, a swallow barium exploration with lateral incidence should look for PVS. Conversely to adults, an endoscopic dilation is frequently necessary to control dysphagia in children.

Prenatal diagnosis of Pierre Robin Sequence: accuracy and ability to predict phenotype and functional severity.

OBJECTIVE: To assess the outcome of fetuses who had sonographic features suggestive of Pierre Robin Sequence (PRS). METHOD: All prenatal ultrasounds that mentioned 'posterior cleft palate', or 'micro or retrognathia' or 'PRS' over 13 and 20 years, respectively, at two obstetrical centers were reviewed. Medical records for children with isolated PRS monitored over 20 years at a PRS referral center for prenatal anomalies and the severity of neonatal feeding and respiratory functional disorders were utilized for comparison. RESULTS: From a prenatal ultrasound database of 166 000 cases, 157 had one or more of the sonographic signs suggestive of PRS and had follow-up available. Of them, 33 (21%) had confirmed PRS, 9 (6%) were normal and 115 (73%) had chromosomal aberrations, associated malformations or neurological anomalies. Visualization of a posterior cleft palate in addition to retro-micrognathia had a positive predictive value of 100% for PRS. The distribution of functional severity grades was similar in cases suspected prenatally as in 238 cases of PRS followed in the referral center in Necker Hospital. CONCLUSION: Only a minority of cases of fetal retrognathia have complete PRS; the majority have other severe conditions. Prenatal prediction of functional severity of isolated PRS is not possible.

Apparent diffusion coefficient measurements of the fetal brain during the third trimester of pregnancy: how reliable are they in clinical practice?

OBJECTIVE: The objective of this study was to determine the reproducibility, the inter-hemispheric difference and the reference apparent diffusion coefficient (ADC) values of the fetal brain according to gestational age. METHOD: One hundred and one normal fetal brain (29.4-38.4 weeks) were analysed with diffusion-weighted MR imaging. ADC was measured in frontal white matter (FWM), occipital white matter (OWM), centrum semi-ovale (CSO), basal ganglia (BG), cerebellar hemisphere (CBM) and pons. ADC ratios (fronto-occipital, fronto-cerebellar and occipito-cerebellar) were calculated. Inter-observer reproducibility was assessed on 27 studies, using intra-class correlation coefficient and Bland-Altman plot. Inter-hemispheric difference was evaluated with Bland-Altman plot. Gestation-specific reference intervals were estimated for each brain region. RESULTS: Inter-observer bias was near zero. Limits of agreement (LOA) were clinically acceptable (-0.17; 0.20 to -0.38; 0.31 × 10(-3) mm(2) /s) for all brain regions except for CSO and pons. Inter-hemispheric bias was near zero. Smallest LOA were for FWM (±0.09 mm(2) /s) and BG (±0.019 mm(2) /s). ADC values decreased, whereas ADC ratio increased with gestational age, reflecting normal maturation. Fronto-occipital, fronto-cerebellar and occipito-cerebellar ratios were consistently above 0.8, 1 and 1, respectively. CONCLUSION: The fetal brain regions with the highest reproducibility and smallest inter-hemispheric differences are the frontal, occipital, cerebellar white matter and BG. ADC ratio could be useful to assess differential temporo-spatial maturation.

Gastrocolic fistula as a complication of a gastric ulcer related to Helicobacter pylori in a child.

Gastrocolic fistulas are very rare in children and their association with Helicobacter pylori is poorly described. We present the case of a 10-year-old boy with a history of chronic abdominal pain, diarrhea, halitosis, and growth delay diagnosed with H. pylori-associated gastritis and gastrocolic fistula. The boy recovered with resection surgery and antibiotic therapy for eradication of the pathogen. This is the first description of a gastrocolic fistula in pediatrics related to H. pylori.

Is fetal cerebral MRI worthwhile in antenatally diagnosed isolated cleft lip with or without palate?

OBJECTIVE: This study aims to evaluate the use of fetal brain magnetic resonance imaging (MRI) following an antenatal sonographic diagnosis of isolated cleft lip with or without cleft palate (CL/P). METHOD: This was a retrospective study of 92 fetuses antenatally diagnosed with isolated CL/P on screening ultrasound. All patients underwent expert diagnostic antenatal ultrasound, fetal brain MRI, and karyotype analysis. RESULTS: Five cases were excluded from the study as associated abnormalities were detected on expert ultrasound: corpus callosum agenesis (n = 1), retrognathism (n = 3), and ectrodactyly (n = 1). Fetal MRI diagnosed unsuspected midline cerebral abnormalities in four out of the 87 remaining cases (4.6%): vermis agenesis (n = 1), isolated arhinencephaly (n = 2), and suspicion of pituitary abnormality (n = 1). All karyotype analyses were normal. CONCLUSION: In CL/P, the incidence of associated cerebral abnormalities overlooked on ultrasound is 4.6%. Careful evaluation of midline structures by expert ultrasound in CL/P is necessary and may be sufficient. MRI can be useful if the US examination is limited or in case of family history. However, the choice to proceed to fetal MRI may vary from institution to institution.

Does the radiographic transition zone correlate with the level of aganglionosis on the specimen in Hirschsprung's disease?

PURPOSE: The correlation between radiographic transition zone on contrast enema in Hirschsprung's disease and the total length of aganglionosis is known to be inaccurate. The aim of our study was to analyse this correlation more precisely to improve preoperative planning of the corrective surgery. METHODS: From 1998 to 2009, 79 patients were operated on for Hirschsprung's disease. All available preoperative contrast enemas (n = 61) had been single blind reviewed by the same radiologist who defined the radiographic transition zone when present in vertebral level. Four groups were determined (rectal, rectosigmoid, long segment, and absence of transition zone) and by Kappa coefficient of agreement correlated to the length of aganglionosis in the pathological report. RESULTS: Radiological findings were concordant with the specimen in pathology in 8 cases of 19 in rectal form (42 %), in 20 cases of 35 in rectosigmoid form (57 %), in all 6 cases of long-segment form (100 %), in the 2 cases of total colonic form (100 %) with a global agreement of 58.1 %, κ = 0.39 CI [0.24; 0.57]. CONCLUSION: Correlation between level of radiographic transition zone on contrast enema and length of aganglionosis remains low. Systematic preoperative biopsy by coelioscopy or ombilical incision is mandatory.

Chronic Recurrent Multifocal Osteomyelitis in Pediatric Crohn Disease, A Paradoxical Effect to Antitumor Necrosis Factor Alpha.

Tumor necrosis factor-α (TNF-α) inhibitors have resulted in significant progress in the treatment of chronic inflammatory diseases. However, these therapies can lead to paradoxical immune-mediated inflammatory diseases with unknown physiopathology. For the first time, we report 3 cases of paradoxical chronic recurrent multifocal osteomyelitis after infliximab or adalimumab therapy during the course of Crohn disease. The patients complained of bone pain without joint involvement. At the time of diagnosis of paradoxical reaction, all patients were in remission due to anti-TNFα efficiency. Trough levels of anti-TNFα were in the expected range, and there were no anti-anti-TNFα antibodies. The duration of treatment was between 2 and 26 months. Other causes of CRMO were excluded. All patients recovered after discontinuation of infliximab (n = 2) or adalimumab (n = 1). The increasing use of these therapies leads to new descriptions of paradoxical effects, which clinicians should be aware of.

Severe Phenotype of Cutis Laxa Type 1B with Antenatal Signs due to a Novel Homozygous Nonsense Mutation in EFEMP2.

EFEMP2 mutations are known to be responsible for autosomal recessive cutis laxa type 1B (ARCL1B), a rare multisystem disease affecting skin, skeleton, and vascular structures. We report 2 additional related cases of ARCL1B of particular severity leading to termination of pregnancy. Cardinal signs of this connective tissue disease were already seen during the second trimester of pregnancy, then confirmed and clarified at autopsy. Anomalies included cutis laxa, arachnodactyly, clubfoot, wormian bones, moderate bowing of long bones with slender bone trabeculae, rib fractures, undermuscularized diaphragm, hiatal hernia, and arterial tortuosity with thick vascular walls and disorganized elastic fibers. Sequencing of the EFEMP2 gene revealed a novel homozygous nonsense mutation: c.639C>A (p.Cys213*). We performed a thorough histological analysis and discuss differential diagnoses, genotype-phenotype correlations, and the challenge of prenatal diagnosis of this disease.

Ileal involvement is age dependent in pediatric Crohn's disease.

BACKGROUND: Lymphoid follicles (LFs) have been suggested to play a role at the early stage of Crohn's disease (CD) lesions. In the small bowel, LFs are grouped, forming Peyer's patches, which develop early in fetal life, grow in size and number until puberty, and undergo involution. In contrast, colonic LFs are isolated and undergo little change during life. As a result, if LFs play a role in the occurrence of CD lesions, the distribution of ileal and colonic lesions is expected to be altered in small children. METHODS: Medical records of 2 independent French (n = 136) and Swedish (n = 55) cohorts of consecutive pediatric CD were reviewed. Disease sites and age of onset were recorded, and the age-dependent probability to develop ileal lesions was computed. The CARD15/NOD2 genotype was also analyzed when available (n = 99). RESULTS: The curves of disease occurrence were significantly different in case of CD with or without ileal lesions (P < 0.0001). At the age of 8 years, the probability (95% confidence interval) of small bowel involvement was 0.19 (0.07-0.39). It increased until 16 years of age to 0.61 (0.54-0.68). It was slightly higher in patients carrying 1 or more CARD15/NOD2 mutations [0.75 (0.55-0.89)] than in wild-type patients [0.46 (0.34-0.58)]. CARD15 mutations also influenced the age of onset of ileal disease (P < 0.02). CONCLUSIONS: In children, ileal CD lesions are delayed compared with colonic lesions. This observation is in agreement with the previously proposed hypothesis of a pathophysiological role of Peyer's patches in ileal CD. The rarity of small bowel lesions should be a warning to be cautious when classifying chronic colitis in small children.

Prenatal pelvic MRI: additional clues for assessment of urogenital obstructive anomalies.

OBJECTIVE: Ultrasound prenatal evaluation of pelvic cystic mass can be challenging. After having ruled out a cloaca anterior to a large hydrocolpos, it is important to differentiate between combined urogenital anomalies such as urogenital sinus and isolated genital anomalies. PATIENTS AND METHODS: We reviewed the charts of 13 women referred for a third trimester pelvic MRI for cystic pelvic mass discovered in second trimester ultrasound. We evaluated MRI compared with postnatal surgical findings in order to determine clues for improving prenatal diagnoses. RESULTS: MRI excluded the diagnosis of cloacal malformation in nine cases with no false negative. Once a cloaca is ruled out, a different signal between the bladder and the hydrocolpos on T2 sequences is in favor of an isolated genital obstruction. In contrast, in case of urogenital sinus, the vagina is filled with a mixture of genital secretions and urine, which gives it an MRI signal similar to the bladder on T2 sequences. CONCLUSION: Third trimester fetal MRI is an essential exam for characterization of pelvic cystic mass diagnosed by ultrasound. This exam appears valuable for invalidating the diagnosis of cloacal malformation and for differentiating between isolated genital obstruction and urogenital sinus.

Cloaca in discordant monoamniotic twins: prenatal diagnosis and consequence for fetal lung development.

Objective Describe a case of cloaca prenatally diagnosed in one of a set of monoamniotic twins. Study Design Retrospective review of a case. Results Cloaca is one of the most complex and severe degrees of anorectal malformations in girls. We present a discordant cloaca in monoamniotic twins. Fetal ultrasound showed a female fetus with a pelvic midline cystic mass, a phallus-like structure, a probable anorectal atresia with absence of anal dimple and a flat perineum, and renal anomalies. The diagnosis was confirmed by fetal magnetic resonance imaging postnatally. Conclusions The rarity of the malformation in a monoamniotic pregnancy, the difficulties of prenatal diagnosis, the pathogenic assumptions, and the consequences of adequate amniotic fluid for fetal lung development are discussed.

Mowat-Wilson syndrome in a fetus with antenatal diagnosis of short corpus callosum: advocacy for standard autopsy.

Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene rarely diagnosed prenatally and with little fetal description reported. It is mainly characterized by moderate-to-severe intellectual disability, epilepsy, facial dysmorphism and various malformations including Hirschsprung disease and corpus callosum anomalies. Here we report a fetal case of MWS well described, suspected at standard autopsy. The association of a corpus callosum hypoplasia with a histological Hirschsprung disease and a typical facial gestalt allowed the guiding of genetic testing. Classical fetopathological examination still keeps indications in cases of syndromic association in the era of virtual autopsy.

Female covered urethral duplication with urogenital sinus.

We report a covered urethral duplication in a girl presenting prenatally with an enlarged fluid-filled vulvar cyst, genital duplication, and urogenital sinus revealed by fetal magnetic resonance imaging (MRI) and serial ultrasounds. Physical examination revealed an enlarged vulvar mass covering the clitoris, a single orifice, and normally sited anus. Congenital adrenal hyperplasia was ruled out at birth. MRI in addition showed an accessory duct between the sinus and the urine-filled vulvar pouch with a bifid clitoris. A total urogenital sinus mobilization with resection of the accessory urethra and vulvoplasty was performed with uneventful follow-up.

Ultrasonography of Crohn disease in children.

US is increasingly performed in Crohn disease (CD) in children as a first line imaging modality. It reduces the use of other more invasive examinations such as endoscopy, CT or contrast enema. We describe bowel ultrasonography technique, normal bowel appearances on US and pathological patterns in CD. We discuss the current role and limitations of bowel US in CD in children including diagnosis, extent of disease, assessment of disease activity, follow-up and detection of complications. The diagnostic accuracy of US is discussed according to the literature and compared to other imaging modalities. US is currently used for screening in children with the suspicion of inflammatory bowel disease (IBD) with a good negative predictive value. In follow-up, US has a role in monitoring medical treatment by evaluating disease activity, extent of disease and for detecting complications.

Bilateral adrenal neuroblastoma and nephroblastoma occurring synchronously in a child with Fanconi's anemia and VACTERL syndrome.

Fanconi's anemia (FA) is an autosomal recessive inherited syndrome with a predisposition to malignancy. The association between FA and solid pediatric tumors is extremely rare. The authors report a rare case of VACTERL syndrome associated with FA and multiple solid pediatric tumors occurring in a very young girl. This child had numerous congenital anomalies (horseshoe kidney, cerebella hypoplasia, microcephaly, sacral agenesis) and esophageal atresia, which was repaired in neonatal period. Such association led quickly to the diagnosis of FA. At age of 11 months, she developed simultaneously a renal tumor in a horseshoe kidney and bilateral adrenal tumors. The left adrenal mass was removed, and partial nephrectomy was performed. Histological analysis concluded to adrenal neuroblastoma and nephroblastoma. We also evaluated the c-kit expression in these tumors to propose a therapeutic alternative to chemotherapy by oral agent STI-571 (Gleevec; Novartis, East Hanover, NJ). Strong cytoplasmic immunostaining of c-kit was found in both tumors. Unfortunately, she quickly developed a posterior cerebellar fossa tumor and died 1 month later. This clinical situation is very rare but suggests that young patients with FA and solid pediatric tumors may belong to a particular subgroup of FA. Further studies are necessary to test if STI-571 treatment could be efficient in such patients with pediatric tumors.