Elaboration of a semi-automated algorithm for brain arteriovenous malformation segmentation: initial results.

OBJECTIVES: The purpose of our study was to distinguish the different components of a brain arteriovenous malformation (bAVM) on 3D rotational angiography (3D-RA) using a semi-automated segmentation algorithm. MATERIALS AND METHODS: Data from 3D-RA of 15 patients (8 males, 7 females; 14 supratentorial bAVMs, 1 infratentorial) were used to test the algorithm. Segmentation was performed in two steps: (1) nidus segmentation from propagation (vertical then horizontal) of tagging on the reference slice (i.e., the slice on which the nidus had the biggest surface); (2) contiguity propagation (based on density and variance) from tagging of arteries and veins distant from the nidus. Segmentation quality was evaluated by comparison with six frame/s DSA by two independent reviewers. Analysis of supraselective microcatheterisation was performed to dispel discrepancy. RESULTS: Mean duration for bAVM segmentation was 64 ± 26 min. Quality of segmentation was evaluated as good or fair in 93% of cases. Segmentation had better results than six frame/s DSA for the depiction of a focal ectasia on the main draining vein and for the evaluation of the venous drainage pattern. CONCLUSION: This segmentation algorithm is a promising tool that may help improve the understanding of bAVM angio-architecture, especially the venous drainage. KEY POINTS: • The segmentation algorithm allows for the distinction of the AVM's components • This algorithm helps to see the venous drainage of bAVMs more precisely • This algorithm may help to reduce the treatment-related complication rate.

A critical review of the classic metaphyseal lesion: traumatic or metabolic?

OBJECTIVE: The purpose of this study was to review the hypothesis that classic metaphyseal lesions represent traumatic changes in abused infants and compare these lesions with healing rickets. MATERIALS AND METHODS: Using a PubMed search, a multidisciplinary team reviewed studies that reported the histopathologic correlation of classic metaphyseal lesions. Selective studies of growth plate injury and rickets were cross-referenced. RESULTS: Nine identified classic metaphyseal lesion studies were performed by the same principal investigator. Control subjects were inadequate. Details of abuse determination and metabolic bone disease exclusion were lacking. The presence of only a single radiology reviewer prevented establishment of interobserver variability. Microscopy was performed by two researchers who were not pathologists. Classic metaphyseal lesions have not been experimentally reproduced and are unrecognized in the accidental trauma literature. The proposed primary spongiosa location is inconsistent with the variable radiographic appearances. Classic metaphyseal lesions were not differentiated from tissue processing artifacts. Bleeding and callus were uncommon in spite of the vascular nature of the metaphysis. The conclusion that excessive hypertrophic chondrocytes secondary to vascular disruption were indicative of fracture healing contradicts the paucity of bleeding, callus, and periosteal reaction. Several similarities exist between classic metaphyseal lesions and healing rickets, including excessive hypertrophic chondrocytes. "Bucket-handle" and "corner fracture" classic metaphyseal lesions resemble healing rickets within the growth plate and the perichondrial ring, respectively. The age of presentation was more typical of bone fragility disorders, including rickets, than reported in prior child abuse series. CONCLUSION: The hypothesis that classic metaphyseal lesions are secondary to child abuse is poorly supported. Their histologic and radiographic features are similar to healing infantile rickets. Until classic metaphyseal lesions are experimentally replicated and independently validated, their traumatic origin remains unsubstantiated.

Metabolic Bone Disease of Infancy in the offspring of mothers with bariatric surgery: A series of 5 infants in contested cases of child abuse.

BACKGROUND AND AIMS: Metabolic Bone Disease of Infancy is a multifactorial disorder of bone fragility in infants who typically present under 6 months of age with multiple unexplained fractures. Major risk factors for this disorder relate to the fetal time period and include decreased provision of the essential nutrients for bone formation during pregnancy (calcium, phosphate, vitamin D, and protein), prematurity, and decreased fetal bone loading. METHODS: This study presents 5 infants with multiple unexplained fractures born to women who had prior bariatric surgery in which child abuse was alleged, and the alleged perpetrator denied wrong doing. RESULTS: The radiographic findings showed poor bone mineralization and were consistent with Metabolic Bone Disease of Infancy. CONCLUSIONS: Using the Utah Paradigm to understand risk factors for MBDI, the authors believe the nutritional deficiencies that accompany bariatric surgery likely contribute to the bone fragility in these 5 infants. Other risk factors for MBDI were appreciated in 4 of the 5 cases. 1,25 dihydroxyvitamin D was elevated or high-normal suggesting calcium deficiency in 2 cases. We believe infants born to mothers who have had prior bariatric surgery are at increased risk for bone fragility and MBDI during the first 6 months of life.

Nutritional rickets and vitamin D deficiency: consequences and strategies for treatment and prevention.

INTRODUCTION: Rickets is typically characterized by bone deformities due to defective bone mineralization and chondrocyte maturation in growing bones. However, infantile rickets often goes unrecognized, because the skeletal abnormalities are more subtle and often can only be detected radiologically. Nutritional rickets is a major public health concern in several regions worldwide. It is most commonly caused by vitamin D and/or calcium deficiency. AREA COVERED: We provide an overview of historical perspective, epidemiology, and pathophysiology of nutritional rickets. Additionally, we outline diagnostic approaches and highlight challenges in radiographic diagnosis of rickets. Finally, we present strategies for prevention and treatment of rickets. EXPERT OPINION: Despite the evidence from clinical databases that rickets is a rare disease, it is likely that rickets is clinically underdiagnosed as studies designed to screen healthy children for radiographic evidence of rickets reported surprisingly much higher prevalence. It has been reported that some of the radiologic features of rickets can be misinterpreted as fractures. To prevent nutritional rickets, most if not all infants and young children, should receive vitamin D from formulas and foods that are fortified with vitamin D or supplementation to achieve a serum 25-hydroxyvitamin D of at least 20 ng/mL as recommended by the Institute of Medicine. It has been recommended by the Endocrine Society that to achieve maximum bone health for children and adults, a serum concentration of 25-hydroxyvitamin D should be at least 30 ng/mL and preferably 40-60 ng/mL. Pregnant women who are unable to obtain an adequate amount of vitamin D from sunlight exposure and natural and fortified diets should take a vitamin D supplement of 1500-2000 IUs daily as recommended by the Endocrine Society since it has been demonstrated that 600 IUs daily will not maintain a circulating 25-hydroxyvitamin D of at least 20 ng/mL and most pregnant women. If lactating women take approximately 6400 IUs of vitamin D daily, they provide enough vitamin D in their milk to satisfy their infant's requirement thereby preventing rickets.

Findings of metabolic bone disease in infants with unexplained fractures in contested child abuse investigations: a case series of 75 infants.

Background Infants who present with multiple unexplained fractures (MUF) are often diagnosed as victims of child abuse when parents deny wrongdoing and cannot provide a plausible alternative explanation. Herein we describe evidence of specific and commonly overlooked radiographic abnormalities and risk factors that suggest a medical explanation in such cases. Methods We evaluated such infants in which we reviewed the radiographs for signs of poor bone mineralization. We reviewed medical, pregnancy and family histories. Results Seventy-five of 78 cases showed poor bone mineralization with findings of healing rickets indicating susceptibility to fragility fractures that could result from a wide variety of causes other than child abuse. We found risk factors that could explain the poor bone mineralization: maternal and infant vitamin D deficiency (VDD), decreased fetal bone loading, prematurity and others. Most infants had more than one risk factor indicating that this bone disorder is a multifactorial disorder that we term metabolic bone disease of infancy (MBDI). Maternal and infant VDD were common. When tested, 1,25-dihydroxyvitamin D levels were often elevated, indicating metabolic bone disease. Conclusions Child abuse is sometimes incorrectly diagnosed in infants with MUF. Appreciation of the radiographic signs of MBDI (healing rickets), risk factors for MBDI and appropriate laboratory testing will improve diagnostic accuracy in these cases.

Genome Mining and Comparative Analysis of Streptococcus intermedius Causing Brain Abscess in a Child.

Streptococcus intermedius (SI) is associated with prolonged hospitalization and low survival rates. The genetic mechanisms involved in brain abscess development and genome evolution in comparison to other members of the Streptococcus anginosus group are understudied. We performed a whole-genome comparative analysis of an SI isolate, LAU_SINT, associated with brain abscess following sinusitis with all SI genomes in addition to S. constellatus and S. anginosus. Selective pressure on virulence factors, phages, pan-genome evolution and single-nucleotide polymorphism analysis were assessed. The structural details of the type seven secretion system (T7SS) was elucidated and compared with different organisms. ily and nanA were both abundant and conserved. Nisin resistance determinants were found in 47% of the isolates. Pan-genome and SNPs-based analysis didn't reveal significant geo-patterns. Our results showed that two SC isolates were misidentified as SI. We propose the presence of four T7SS modules (I⁻IV) located on various genomic islands. We detected a variety of factors linked to metal ions binding on the GIs carrying T7SS. This is the first detailed report characterizing the T7SS and its link to nisin resistance and metal ions binding in SI. These and yet uncharacterized T7SS transmembrane proteins merit further studies and could represent potential therapeutic targets.

Essential role of ATP6AP2 enrichment in caveolae/lipid raft microdomains for the induction of neuronal differentiation of stem cells.

BACKGROUND: The subcellular distribution of prorenin receptor and adaptor protein ATP6AP2 may affect neurogenesis. In this study, we hypothesized that ATP6AP2 expression and subcellular relocalization from caveolae/lipid raft microdomains (CLR-Ms) to intracellular sites may correlate with neuronal differentiation (Neu-Dif) of adipose-derived mesenchymal stem cells (ADSCs). METHODS: Human ADSCs isolated from 24 healthy donors and 24 patients with neurological disorders (ND) were cultured and induced for Neu-Dif. The mechanism of action of ATP6AP2 and the impact of its localization within the plasma membrane (particularly CLR-Ms) and intracellular sites on several pathways (mitogen-activated protein kinase, Wnt(s) signaling and others) and intracellular calcium and exosome release were evaluated. The impact of CLR-Ms on ATP6AP2 or vice versa was determined by pharmacological disruption of CLR-Ms or siATP6AP2 assays. RESULTS: In patients with ND, loss of ATP6AP2 from CLR-Ms correlated with an inhibition of Neu-Dif and signaling. However, its relocalization in CLR-Ms was positively correlated to induction of Neu-Dif in healthy subjects. An apparent switch from canonical to noncanonical Wnt signaling as well as from caveolin to flotillin occurs concurrently with the increases of ATP6AP2 expression during neurogenesis. Stimulation by renin activates ERK/JNK/CREB/c-Jun but failed to induce ß-catenin. Wnt5a enhanced the renin-induced JNK responsiveness. Gα proteins crosslink ATP6AP2 to caveolin where a switch from Gαi to Gαq is necessary for Neu-Dif. In ATP6AP2-enriched CLR-Ms, the release of exosomes was induced dependently from the intracellular Ca2+ and Gαq. Pharmacological disruption of CLR-M formation/stability impairs both ATP6AP2 localization and Neu-Dif in addition to reducing exosome release, indicating an essential role of ATP6AP2 enrichment in CLR-Ms for the induction of Neu-Dif. The mechanism is dependent on CLR-M dynamics, particularly the membrane fluidity. Knockdown of ATP6AP2 inhibited Neu-Dif but increased astrocytic-Dif, depleted ATP6AP2/flotillin/Gαq but accumulated caveolin/Gαi in CLR-Ms, and blocked the activation of JNK/ERK/c-Jun/CREB/exosome release. siATP6AP2 cells treated with sphingomyelinase/methyl-ß-cyclodextrin reversed the levels of caveolin/flotillin in CLR-Ms but did not induce Neu-Dif, indicating the crucial relocalization of ATP6AP2 in CLR-Ms for neurogenesis. Treatment of ND-derived cells with nSMase showed reversibility in ATP6AP2 abundance in CLR-Ms and enhanced Neu-Dif. CONCLUSIONS: This study gives evidence of the determinant role of CLR-M ATP6AP2 localization for neuronal and oligodendrocyte differentiation involving mechanisms of switches from Gαi/caveolin/canonical to Gαq/flotillin/PCP, the ERK/JNK pathway and Ca2+-dependent release of exosomes and as a potential target of drug therapy for neurodegenerative disorders.

Interest of convex spherical anamorphosis in better understanding of brain AVMs' angioarchitecture.

INTRODUCTION: Convex spherical anamorphosis is a barrel distortion that consists of the application of a plane surface on a convex hemisphere. Applied in vascular imaging of brain arteriovenous malformations (bAVMs), this deformation may help to 'spread' the nidus and surrounding vessels (arteries/veins) and thus to differentiate the different components of bAVMs more accurately. METHODS: The imaging data from 15 patients (8 male, 7 female; 14 supratentorial bAVMs, 1 infratentorial) were used to test the algorithm. The algorithm was applied to three-dimensional rotational angiography (3D-RA) volume rendering reconstructions in anteroposterior, lateral and oblique views and compared with regular 3D-RA and DSA. Arterial feeder and draining vein count and quality visualization of the main draining vein and intranidal aneurysms were compared between the three imaging techniques. RESULTS: Anamorphosis was able to depict more arterial feeders than 3D-RA alone (p=0.027). There was no statistically significant difference between 6 f/s DSA and anamorphosis for arterial feeder count. No difference was observed in draining vein count between the three imaging modalities. Visualization of the precise origin of the main draining vein was considered to be good in 67% of the cases with anamorphosis versus 47% and 33% for 6 f/s DSA and 3D-RA alone, respectively. Intranidal aneurysms were accurately depicted by anamorphosis (2 cases), whereas 6 f/s DSA and 3D-RA showed doubtful images in one and two additional cases, respectively, which were finally confirmed as focal venous ectasias on supraselective injection. CONCLUSIONS: Anamorphosis can help to visualize more precisely the main draining vein origin of the bAVM and depict more accurately intranidal aneurysms.

Congenital rickets due to vitamin D deficiency in the mothers.

BACKGROUND & AIMS: We wished to review all published reports of congenital rickets to identify the causes and characteristics. METHODS: 25 cases were identified in 19 published reports in which there was radiological and/or histological evidence of rickets in the first two weeks after birth. Cases of rickets associated with maternal renal failure were excluded as were infants born at less than 32 weeks gestation. RESULTS: There was evidence of maternal deficiency in 24 of these cases. In 16 cases the diagnosis of the rickets led to the identification of symptomatic osteomalacia in the mothers. Of the 12 mothers who had assays for serum 25-hydroxyvitamin D (25OHD) 11 had values less than 10 ng/mL. Presentations in the infants included craniotabes, wide skull sutures, rachitic rosaries, enlargement of the wrists, tetany and convulsions. In two cases rickets had been suspected from antenatal X-rays. In five cases fractures were found at the time of initial presentation. Of the 16 infants with serum calcium assays 15 had values lower than 8.8 mg/dL. Of 13 infants who had serum alkaline phosphatase assays 12 had abnormally high levels. Of the seven infants in whom serum 25OHD was measured before treatment, all had values less than 10 ng/mL. CONCLUSIONS: These reports provide strong support for the view that maternal deficiency leads to overt bone disease from before birth. Maternal deficiency probably also leads to impairment of bone quality in postnatal life. The importance of ensuring adequate vitamin D nutrition in pregnancy is emphasised.

Endovascular exclusion of the anterior communicating artery with flow-diverter stents as an emergency treatment for blister-like intracranial aneurysms. A case report.

Blood blister-like aneurysms (BLAs) are rare lesions, associated with diffuse subarachnoid hemorrhage (SAH). BLAs tend to rebleed quickly after first bleeding and must be treated as an emergency. Acute treatment is challenging using surgical and endovascular approaches due to the fragile aneurysm wall and small sac. Flow-diverter stents (FDSs) may offer a new option for the treatment of difficult small aneurysms. We describe a case of a ruptured BLA on the anterior communicating artery (AComA) treated in the acute phase of SAH by endovascular exclusion of the AComA with deployment of two FDSs in the A1/A2 junctions of both anterior cerebral arteries (ACAs). A 61-year-old man was admitted for diffuse SAH with a focal interhemispheric hematoma. Angiography revealed multiple arterial wall irregularities on the AComA and both ACAs. We performed an endovascular shunt of the AComA by deploying two FDSs in both A1/A2 junctions. Immediate control injections confirmed flow diversion in the A1/A2 segments of the ACAs with decreased blood flow in the AComA. The patient's course in hospital was uneventful. A three-month follow-up angiogram confirmed complete exclusion of the aneurysms, complete exclusion of the AComA, and patency of the two ACAs without any persistent arterial wall irregularity. Endovascular bypass using an FDS for a ruptured BLA has never been described. It establishes a new therapeutic option despite the need for antiplatelet therapy. Endovascular AComA exclusion using an FDS may be a solution when no other treatment is available for a ruptured BLA.

Embolization of spinal dural arteriovenous fistula via the retrocorporeal artery: case report.

BACKGROUND AND IMPORTANCE: The goal of spinal dural arteriovenous fistula (DAVF) treatment is to permanently occlude the proximal draining vein and the fistula itself, which can be achieved by open surgery or endovascular treatment. The endovascular approach is currently the primary treatment, but it requires the presence of an access as close to the site of the fistula as possible. This case illustrates that the retrocorporeal artery may be an alternative option in case of previous embolization failure with proximal occlusion of the radicular arteries. CLINICAL PRESENTATION: A 54-year-old man presented with an 18-month history of progressive paraparesis secondary to right L2 spinal DAVF. The first endovascular treatment failed to achieve occlusion of the fistula via the ipsilateral L2 and L3 radicular arteries. Given the proximal occlusion of these feeders during the first embolization, the dilated retrocorporeal arteries were approached via the contralateral L2 and L3 radicular arteries. Complete occlusion of the fistula was achieved with Onyx in a single session with progressive improvement of preoperative neurological deficit. CONCLUSION: The retrocorporeal artery may provide a safe alternative approach to spinal DAVFs in cases in which a conventional endovascular approach failed, thus avoiding invasive surgical treatment.