Publications by authors named "Volodia Dangouloff-Ros"

21 Publications

  • Page 1 of 1

Pineal alveolar rhabdomyosarcoma with PAX3:NCOA2 fusion inducing OLIG2 sexpression, a potential pitfall in the central nervous system.

Histopathology 2021 Mar 5. Epub 2021 Mar 5.

Department of Neuropathology, GHU Paris-Neurosciences, Sainte-Anne Hospital, 75014, Paris, France.

A previously healthy 12-year-old boy began experiencing intracranial hypertension symptoms. Cerebral magnetic resonance imaging (MRI) showed a pineal mass. Cerebrospinal fluid and blood tested negative for β-human chorionic gonadotrophin, α-foetoprotein, carcinoembryonic antigen, and placental alkaline phosphatase.
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http://dx.doi.org/10.1111/his.14364DOI Listing
March 2021

Arterial spin labeling brain MRI study to evaluate the impact of deafness on cerebral perfusion in 79 children before cochlear implantation.

Neuroimage Clin 2021 27;29:102510. Epub 2020 Nov 27.

Service de radiologie pédiatrique, Hôpital Necker Enfants Malades, Assistance Publique Hôpitaux de Paris, APHP, Université de Paris, INSERM U1163, Institut Imagine, Paris, France; INSERM ERL "Developmental Trajectories & Psychiatry", Université Paris Saclay, Ecole Normale Supérieure Paris-Saclay, Université de Paris, CNRS, Centre Borelli, France.

Age at implantation is considered to be a major factor, influencing outcomes after pediatric cochlear implantation. In the absence of acoustic input, it has been proposed that cross-modal reorganization can be detrimental for adaptation to the new electrical input provided by a cochlear implant. Here, through a retrospective study, we aimed to investigate differences in cerebral blood flow (CBF) at rest prior to implantation in children with congenital deafness compared to normally hearing children. In addition, we looked at the putative link between pre-operative rest-CBF and the oral intelligibility scores at 12 months post-implantation. Finally, we observed the evolution of perfusion with age, within brain areas showing abnormal rest-CBF associated to deafness, in deaf children and in normally hearing children. In children older than 5 years old, results showed a significant bilateral hypoperfusion in temporal regions in deaf children, particularly in Heschl's gyrus, and a significant hyperperfusion of occipital regions. Furthermore, in children older than 5 years old, whole brain voxel-by-voxel correlation analysis between pre-operative rest-CBF and oral intelligibility scores at 12 months post-implantation, showed significant negative correlation localized in the occipital regions: children who performed worse in the speech perception test one year after implantation were those presenting higher preoperative CBF values in these occipital regions. Finally, when comparing mean relative perfusion (extracted from the temporal regions found abnormal on whole-brain voxel-based analysis) across ages in patients and controls, we observed that the temporal perfusion evolution was significantly different in deaf children than in normally hearing children. Indeed, while temporal perfusion increased with age in normally hearing children, it remained stable in deaf children. We showed a critical period around 4 years old, where in the context of auditory deprivation, there is a lack of synaptic activity in auditory regions. These results support the benefits of early cochlear implantation to maximize the effectiveness of auditory rehabilitation and to avoid cross-modal reorganization.
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http://dx.doi.org/10.1016/j.nicl.2020.102510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7777537PMC
November 2020

Complete hemispherotomy leads to lateralized functional organization and lower level of consciousness in the isolated hemisphere.

Epilepsia Open 2020 Dec 24;5(4):537-549. Epub 2020 Sep 24.

Assistance Publique Hôpitaux de Paris Hôpital Necker-Enfants Malades Paris France.

Objective: To quantify whole-brain functional organization after complete hemispherotomy, characterizing unexplored plasticity pathways and the conscious level of the dissected hemispheres.

Methods: Evaluation with multimodal magnetic resonance imaging in two pediatric patients undergoing right hemispherotomy including complete callosotomy with a perithalamic section. Regional cerebral blood flow and fMRI network connectivity assessed the functional integrity of both hemispheres after surgery. The level of consciousness was tested by means of a support vector machine classifier which compared the intrinsic organization of the dissected hemispheres with those of patients suffering from disorders of consciousness.

Results: After hemispherotomy, both patients showed typical daily functionality. We found no interhemispheric transfer of functional connectivity in either patient as predicted by the operation. The healthy left hemispheres displayed focal blood hyperperfusion in motor and limbic areas, with preserved network-level organization. Unexpectedly, the disconnected right hemispheres showed sustained network organization despite low regional cerebral blood flow. Subcortically, functional connectivity was increased in the left thalamo-cortical loop and between the cerebelli. One patient further showed unusual ipsilateral right cerebello-cortical connectivity, which was explained by the mediation of the vascular system. The healthy left hemisphere had higher probability to be classified as in a minimally conscious state compared to the isolated right hemisphere.

Significance: Complete hemispherotomy leads to a lateralized whole-brain organization, with the remaining hemisphere claiming most of the brain's energetic reserves supported by subcortical structures. Our results further underline the contribution of nonneuronal vascular signals on contralateral connectivity, shedding light on the nature of network organization in the isolated tissue. The disconnected hemisphere is characterized by a level of consciousness which is necessary but insufficient for conscious processing, paving the way for more specific inquiries about its role in awareness in the absence of behavioral output.
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http://dx.doi.org/10.1002/epi4.12433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733653PMC
December 2020

Rest Functional Brain Maturation during the First Year of Life.

Cereb Cortex 2021 Feb;31(3):1776-1785

INSERM UA10, Department of Pediatric Radiology, Hôpital Necker Enfants Malades, AP-HP, Imagine Institute (UMR 1163), Paris Descartes University, Sorbonne Paris Cité University, Paris 75015, France.

The first year of life is a key period of brain development, characterized by dramatic structural and functional modifications. Here, we measured rest cerebral blood flow (CBF) modifications throughout babies' first year of life using arterial spin labeling magnetic resonance imaging sequence in 52 infants, from 3 to 12 months of age. Overall, global rest CBF significantly increased during this age span. In addition, we found marked regional differences in local functional brain maturation. While primary sensorimotor cortices and insula showed early maturation, temporal and prefrontal region presented great rest CBF increase across the first year of life. Moreover, we highlighted a late and remarkably synchronous maturation of the prefrontal and posterior superior temporal cortices. These different patterns of regional cortical rest CBF modifications reflect a timetable of local functional brain maturation and are consistent with baby's cognitive development within the first year of life.
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http://dx.doi.org/10.1093/cercor/bhaa325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869100PMC
February 2021

Embryonal tumor with multilayered rosettes, -altered with sarcomatous differentiation: histopathologic and molecular characterization of one case.

Clin Neuropathol 2021 Jan-Feb;40(1):11-16

Embryonal tumor with multilayered rosettes, constitutes an aggressive and rare pediatric embryonal tumor of the central nervous system characterized by alterations of the locus at 19q13.12. Embryonal tumors with multilayered rosettes (ETMRs) span a broad histopathological spectrum with primitive neural features and abundant neuropil. Before the molecular definition of this entity, exceptional cases with heterologous differentiation have been evidenced in the literature. Herein, we report the first case of an ETMR featuring a sarcomatous component with proven alteration in both components by an in situ hybridization analysis. This data supports the hypothesis of a divergent differentiation of tumoral cells in this case.
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http://dx.doi.org/10.5414/NP301274DOI Listing
December 2020

Intracranial chondromas: A histopathologic and molecular study of three cases.

Clin Neuropathol 2020 Jul/Aug;39(4):171-178

Aims: Meningeal chondromas constitute a small fraction of central nervous system tumors, with only 61 cases reported in the literature. Somatic mutations of genes have been described in enchondromas, and, in soft-tissue chondromas, rearrangements of the gene have been reported. The aim of our study was to perform molecular analyses of 3 additional cases and to do a complete review of the literature to better characterize this rare entity.

Materials And Methods: Here, we report 3 cases of primitive meningeal chondromas in children and young adults. Immunohistochemical analyses for HMGA2 and IDH1R132H, molecular analyses of mutations, and FISH analysis of the locus were performed.

Results: Immunohistochemical analyses of all cases were negative for IDH1R132H and HMGA2 proteins. Molecular analyses failed to reveal mutations, and FISH analyses did not evidence any rearrangements. Similarly to what is reported in the literature, the 3 meningeal chondromas in this study were benign tumors with no recurrence after complete resection with a follow-up of 85, 46, and 89 months.

Conclusion: Meningeal chondroma is rare. It affects predominantly young adults and has a good outcome. No molecular alterations have currently been described in this entity.
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http://dx.doi.org/10.5414/NP301238DOI Listing
June 2020

EANO-EURACAN clinical practice guideline for diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma.

Lancet Oncol 2019 12;20(12):e715-e728

Wilhelm Sander-NeuroOncology Unit and Department of Neurology, University Hospital Regensburg, Regensburg, Germany. Electronic address:

The European Association of Neuro-Oncology (EANO) and EUropean RAre CANcer (EURACAN) guideline provides recommendations for the diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma. The guideline is based on the 2016 WHO classification of tumours of the CNS and on scientific developments published since 1980. It aims to provide direction for diagnostic and management decisions, and for limiting unnecessary treatments and cost. In view of the scarcity of data in adults with medulloblastoma, we base our recommendations on adult data when possible, but also include recommendations derived from paediatric data if justified. Our recommendations are a resource for professionals involved in the management of post-pubertal and adult patients with medulloblastoma, for patients and caregivers, and for health-care providers in Europe. The implementation of this guideline requires multidisciplinary structures of care, and defined processes of diagnosis and treatment.
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http://dx.doi.org/10.1016/S1470-2045(19)30669-2DOI Listing
December 2019

The histomolecular criteria established for adult anaplastic pilocytic astrocytoma are not applicable to the pediatric population.

Acta Neuropathol 2020 02 1;139(2):287-303. Epub 2019 Nov 1.

Department of Neuropathology, GHU Paris-Neurosciences Sainte-Anne, 1 rue Cabanis, 75014, Paris, France.

Pilocytic astrocytoma (PA) is the most common pediatric glioma, arising from a single driver MAPK pathway alteration. Classified as a grade I tumor according to the 2016 WHO classification, prognosis is excellent with a 10-year survival rate > 95% after surgery. However, rare cases present with anaplastic features, including an unexpected high mitotic/proliferative index, thus posing a diagnostic and therapeutic challenge. Based on small histomolecular series and case reports, such tumors arising at the time of diagnosis or recurrence have been designated by many names including pilocytic astrocytoma with anaplastic features (PAAF). Recent DNA methylation-profiling studies performed mainly on adult cases have revealed that PAAF exhibit a specific methylation signature, thus constituting a distinct methylation class from typical PA [methylation class anaplastic astrocytoma with piloid features-(MC-AAP)]. However, the diagnostic and prognostic significance of MC-AAP remains to be determined in children. We performed an integrative work on the largest pediatric cohort of PAAF, defined according to strict criteria: morphology compatible with the diagnosis of PA, with or without necrosis, ≥ 4 mitoses for 2.3 mm, and MAPK pathway alteration. We subjected 31 tumors to clinical, imaging, morphological and molecular analyses, including DNA methylation profiling. We identified only one tumor belonging to the MC-AAP (3%), the others exhibiting a methylation profile typical for PA (77%), IDH-wild-type glioblastoma (7%), and diffuse leptomeningeal glioneuronal tumor (3%), while three cases (10%) did not match to a known DNA methylation class. No significant outcome differences were observed between PAAF with necrosis versus no necrosis (p = 0.07), or with 4-6 mitoses versus 7 or more mitoses (p = 0.857). Our findings argue that the diagnostic histomolecular criteria established for anaplasia in adult PA are not of diagnostic or prognostic value in a pediatric setting. Further extensive and comprehensive integrative studies are necessary to accurately define this exceptional entity in children.
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http://dx.doi.org/10.1007/s00401-019-02088-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989446PMC
February 2020

High Prevalence of Developmental Venous Anomaly in Diffuse Intrinsic Pontine Gliomas: A Pediatric Control Study.

Neurosurgery 2020 04;86(4):517-523

Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Background: No link has been demonstrated between diffuse intrinsic pontine glioma and developmental venous anomaly in pediatric patients.

Objective: To determine the prevalence of developmental venous anomaly in a pediatric cohort of diffuse intrinsic pontine glioma.

Methods: We performed a retrospective cohort study (1998-2017) of consecutive pediatric patients harboring a diffuse intrinsic pontine glioma (experimental set, n = 162) or a craniopharyngioma (control set, n = 142) in a tertiary pediatric neurosurgical center. The inclusion criteria were the following: age <18 yr at diagnosis; histopathological diagnosis of diffuse intrinsic pontine glioma or craniopharyngioma according to the 2016 World Health Organization classification of tumors of the central nervous system; no previous oncological treatment; and available preoperative magnetic resonance imaging performed with similar acquisition protocol.

Results: We found a significantly higher prevalence of developmental venous anomaly in the experimental set of 162 diffuse intrinsic pontine gliomas (24.1%) than in the control set of 142 craniopharyngiomas (10.6%; P = .001). The prevalence of developmental venous anomalies was not significantly impacted by demographic data (sex, age at diagnosis, and underlying pathological condition), biomolecular analysis (H3-K27M-mutant subgroup, H3.1-K27M-mutant subgroup, and H3.3-K27M-mutant subgroup), or imaging findings (anatomic location, anatomic extension, side, and obstructive hydrocephalus) of the studied diffuse intrinsic pontine gliomas.

Conclusion: We report a higher prevalence of developmental venous anomaly in pediatric diffuse intrinsic pontine glioma patients than in control patients, which suggests a potential underlying common predisposition or a causal relationship that will require deeper investigations.
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http://dx.doi.org/10.1093/neuros/nyz298DOI Listing
April 2020

Neural and behavioral signature of human social perception.

Sci Rep 2019 06 25;9(1):9252. Epub 2019 Jun 25.

INSERM U1000, Department of Pediatric Radiology and IMAGINE Institute, INSERM UMR 1163, Paris Descartes University, Sorbonne Paris Cité, Hôpital Necker-Enfants Malades, Paris, France.

Social behavior is extremely variable among individuals, and the neural basis of this variability is still poorly understood. In this study, we aimed to investigate the neural basis of interindividual variability in the first step of social behavior, that is, social perception. For that purpose, we first used eye-tracking to measure social perception during the passive visualization of socially relevant movie clips. Second, we correlated eye-tracking data with measures of rest cerebral blood flow (CBF) obtained using arterial spin-labeling (ASL) MRI, an index of local rest brain function. The results showed a large interindividual variability in the number of fixations to the eyes of characters during passive visualization of movie clips displaying social interactions. Moreover, individual patterns remained stable across time, suggesting an individual signature of social behavior. Whole-brain analyses showed significant positive correlation between the number of fixations to the eyes and rest CBF: individuals who looked more to the eyes were those with higher rest CBF levels within the right superior temporal regions. Our results indicate the existence of a neural and behavioral signature associated with the interindividual variability in social perception.
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http://dx.doi.org/10.1038/s41598-019-44977-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593101PMC
June 2019

Aortic atresia and interrupted aortic arch communicating through external carotid anastomosis.

Cardiol Young 2019 May 24;29(5):699-700. Epub 2019 May 24.

Department of Pediatric Radiology,Hôpital Universitaire Necker Enfants Malades,AP-HP, 149 rue de Sèvres, 75105 Paris,France.

We describe the case of a newborn girl who displayed association of aortic atresia and interrupted aortic arch, with retrograde flow in ascending aorta, through extracranial anastomoses between vertebral arteries (arisen from descending aorta) and external carotids.
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http://dx.doi.org/10.1017/S1047951119000908DOI Listing
May 2019

Arterial Spin Labeling and Central Precocious Puberty.

Clin Neuroradiol 2020 Mar 5;30(1):137-144. Epub 2018 Nov 5.

Department of Pediatric Radiology, Hôpital Necker Enfants Malades, AP-HP, 149 rue de sèvres, 75015, Paris, France.

Purpose: To evaluate a non-invasive method to assess the progressivity of idiopathic central precocious puberty (CPP) by quantifying perfusion of the pituitary stalk with arterial spin labeling (ASL) and using the gonadotropin-releasing hormone (GnRH) test as a reference test to define progressive CPP.

Methods: In a single center retrospective study, 52 consecutive patients, observed between October 2015 and April 2017 and referred with early signs of puberty, were evaluated using the GnRH test and cerebral magnetic resonance imaging (MRI). Patients with peripheral or non-idiopathic puberty were excluded. The distribution of perfusion values between patients with progressive and non-progressive CPP was compared using a nonparametric Mann-Whitney U‑test.

Results: In this study 35 patients were included and 29 had progressive CPP. These patients displayed significantly higher cerebral blood flow (CBF) values than the 6 patients with non-progressive CPP (p = 0.006). The median CBF for patients with non-progressive and progressive CPP was 45.25 ml/min/100 g (interquartile range 36.9-54) vs. 65 ml/min/100 g (interquartile range 55.5-74.5), respectively. To determine if the CPP was progressive, the best CBF threshold was 55.5 ml/min/100 g with a sensitivity of 76%, a specificity of 83% and an accuracy of 77%. There were strong significant correlations between CBF and LH peak (r = 0.67, p < 0.001) and between CBF and LH/FSH peaks ratio [r = 0.71, p < 0.001] during the GnRH test.

Conclusion: Arterial spin labelling (ASL) offers a novel tool to assess the progressivity of idiopathic CPP.
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http://dx.doi.org/10.1007/s00062-018-0738-5DOI Listing
March 2020

Historadiological correlations in high-grade glioma with the histone 3.3 G34R mutation.

J Neuroradiol 2018 Sep 2;45(5):316-322. Epub 2018 Mar 2.

Department of Pathology, Sainte-Anne Hospital, université Paris-Descartes, U1000, France.

Background And Purpose: Molecular alterations were recently added to the World Health Organization (WHO) 2016 classification of central nervous system (CNS) tumors. We correlated the histological and radiological features of G34R mutant high-grade gliomas, a recently described hemispheric and supratentorial glioma of children and young adults.

Materials And Methods: We performed a retrospective multicenter study on the histopathological and MRI results of 12 patients.

Results: All tumors were supratentorial. Several radiological aspects were observed. Height over 12 were bulky and well delineated tumors, without visible peritumoral infiltration on MRI and pathologically characterized by highly cellular tissue associated with a moderate peritumoral infiltrative component. Two tumors were ill-defined and hyperintense on T2 sequences and pathologically characterized by diffuse tumoral infiltration. Two tumors were bulky and well delineated with an infiltrative component, both radiologically and histopathologically.

Conclusions: These different patterns may correspond to different pathological mechanisms and a potential link with prognosis should be assessed in further studies.
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http://dx.doi.org/10.1016/j.neurad.2018.02.006DOI Listing
September 2018

High predictive value of brain MRI imaging in primary mitochondrial respiratory chain deficiency.

J Med Genet 2018 Jun 22;55(6):378-383. Epub 2018 Jan 22.

Department of Pediatric Radiology, INSERM UMR 1163 and INSERM U1000, Paris Descartes University, Sorbonne Paris Cité, Hôpital Necker-Enfants Malades, Paris, France.

Background: Because the mitochondrial respiratory chain (RC) is ubiquitous, its deficiency can theoretically give rise to any symptom in any organ or tissue at any age with any mode of inheritance, owing to the twofold genetic origin of respiratory enzyme machinery, that is, nuclear and mitochondrial. Not all respiratory enzyme deficiencies are primary and secondary or artefactual deficiency is frequently observed, leading to a number of misleading conclusions and inappropriate investigations in clinical practice. This study is aimed at investigating the potential role of brain MRI in distinguishing primary RC deficiency from phenocopies and other aetiologies.

Methods: Starting from a large series of 189 patients (median age: 3.5 years (8 days-56 years), 58% males) showing signs of RC enzyme deficiency, for whom both brain MRIs and disease-causing mutations were available, we retrospectively studied the positive predictive value (PPV) and the positive likelihood ratio (LR+) of brain MRI imaging and its ability to discriminate between two groups: primary deficiency of the mitochondrial RC machinery and phenocopies.

Results: Detection of (1) brainstem hyperintensity with basal ganglia involvement (P≤0.001) and (2) lactate peak with either brainstem or basal ganglia hyperintensity was highly suggestive of primary RC deficiency (P≤0.01). Fourteen items had a PPV>95% and LR+ was greater than 9 for seven signs. Biallelic mutations represented the main differential diagnosis. Non-significant differences between the two groups were found for cortical/subcortical atrophy, leucoencephalopathy and involvement of caudate nuclei, spinothalamic tract and corpus callosum.

Conclusion: Based on these results and owing to invasiveness of skeletal muscle biopsies and cost of high-throughput DNA sequencing, we suggest giving consideration to brain MRI imaging as a diagnostic marker and an informative investigation to be performed in patients showing signs of RC enzyme deficiency.
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http://dx.doi.org/10.1136/jmedgenet-2017-105094DOI Listing
June 2018

Cerebral blood flow changes after radiation therapy identifies pseudoprogression in diffuse intrinsic pontine gliomas.

Neuro Oncol 2018 06;20(7):994-1002

Hôpital Necker Enfants Malades, Pediatric Radiology Department, Paris, France.

Background: The interval between progression and death in diffuse intrinsic pontine glioma (DIPG) is usually <6 months. However, reports of longer patient survival following radiotherapy, in the presence of radiological signs of progression, suggest that these cases may be comparable to pseudoprogression observed in adult glioblastoma. Our aim was to identify such cases and compare their multimodal MRI features with those of patients who did not present the same evolution.

Methods: Multimodal MRIs of 43 children treated for DIPG were retrospectively selected at 4 timepoints: baseline, after radiotherapy, during true progression, and at the last visit. The patients were divided into 2 groups depending on whether they presented conventional MRI changes that mimicked progression. The apparent diffusion coefficient, arterial spin labeling cerebral blood flow (ASL-CBF), and dynamic susceptibility contrast perfusion relative cerebral blood volume (DSCrCBV) and flow (DSCrCBF) values were recorded for each tumor voxel, avoiding necrotic areas.

Results: After radiotherapy, 19 patients (44%) showed radiological signs that mimicked progression: 16 survived >6 months following so-called pseudoprogression, with a median of 8.9 months and a maximum of 35.6 months. All 43 patients exhibited increased blood volume and flow after radiotherapy, but the 90th percentile of those with signs of pseudoprogression had a greater increase of ASL-CBF (P < 0.001). Survival between the 2 groups did not differ significantly. During true progression, DSCrCBF and DSCrCBV values increased only in patients who had not experienced pseudoprogression.

Conclusions: Pseudoprogression is a frequent phenomenon in DIPG patients. This condition needs to be recognized before considering treatment discontinuation. In this study, the larger increase of the ASL-CBF ratio after radiotherapy accurately distinguished pseudoprogression from true progression.
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http://dx.doi.org/10.1093/neuonc/nox227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007230PMC
June 2018

Severe neuroimaging anomalies are usually associated with random X inactivation in leucocytes circulating DNA in X-linked dominant Incontinentia Pigmenti.

Mol Genet Metab 2017 11 10;122(3):140-144. Epub 2017 Jul 10.

Department of Pediatric Radiology, Hôpital Necker Enfants Malades, AP-HP, 149 rue de Sèvres, 75105 Paris, France; INSERM U1000, 149 rue de Sèvres, 75015 Paris, France; UMR 1163, Institut Imagine, 24 boulevard du Montparnasse, 75015 Paris, France; University René Descartes, PRES Sorbonne Paris Cité, 12 rue de l'Ecole de Médecine, Paris, France.

Incontinentia Pigmenti (IP) is a skin disorder with neurological impairment in 30% of cases. The most common disease causing mutation is a deletion of exons 4-10 of the IKBKG gene, located on chromosome Xq28, with skewed X-chromosome inactivation in females, but few cases of random X-inactivation have been reported. We have correlated brain anomalies with X-chromosome inactivation status determined on leucocytes circulating DNA. We reviewed MRI of 18 girls with genetically proven IP. We found three patterns of MRI, normal MRI (n=5), mild white matter abnormalities with cortical and corpus callosum atrophy (n=6), and severe cortical abnormalities suggesting a vascular disease (n=7). Most patients with severe abnormalities had random X-inactivation (6/7,86%), while 80% (4/5) of patients with normal MRI and 100% (6/6) of patients with mild white matter abnormalities had skewed inactivation. These results suggest that skewed chromosome X-inactivation may protect brain from damage, while in case of random inactivation, expression of the mutated IKBKG gene may lead to severe brain lesions.
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http://dx.doi.org/10.1016/j.ymgme.2017.07.001DOI Listing
November 2017

Genomic diagnostics leading to the identification of a TFG-ROS1 fusion in a child with possible atypical meningioma.

Cancer Genet 2017 04 22;212-213:32-37. Epub 2017 Mar 22.

Department of Paediatrics and Adolescent Medicine, Neuroscience Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Meningiomas are rare in children. They are highly complex, harboring unique clinical and pathological characteristics, and many occur in patients with neurofibromatosis type 2. Hereby, we present a case of a two-year-old boy presented with a diagnostically challenging intraventricular tumor. It was incompletely resected 6 times over 14 months but kept progressing and was ultimately deemed unresectable. Histologically, the tumor was initially classified as schwannoma, but extensive international review concluded it was most likely an atypical meningioma, WHO grade II. Comprehensive genomic profiling revealed a TFG-ROS1 fusion, suggesting that ROS1-signaling pathway alterations were driving the tumor growth. In light of this new information, the possibility of a diagnosis of inflammatory myofibroblastic tumor was considered; however the histopathological results were not conclusive. This specific molecular finding allowed the potential use of precision medicine and the patient was enrolled in the AcSé phase 2 trial with crizotinib (NCT02034981), leading to a prolonged partial tumor response which is persisting since 14 months. This case highlights the value of precision cancer medicine in children.
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http://dx.doi.org/10.1016/j.cancergen.2017.03.005DOI Listing
April 2017

Arterial Spin Labeling to Predict Brain Tumor Grading in Children: Correlations between Histopathologic Vascular Density and Perfusion MR Imaging.

Radiology 2016 Nov 3;281(2):553-566. Epub 2016 Jun 3.

From the Department of Pediatric Radiology, Hôpital Necker Enfants Malades, AP-HP, 149 rue de Sèvres, 75105 Paris, France (V.D., E.S., D.G., R.C., F.B., N.B.); INSERM U1000, Paris, France (V.D., D.G., R.C., F.B., P.V., N.B.); IMNC, UMR 8165 CNRS, University Paris Diderot and University Paris Sud, Campus d'Orsay, Orsay, France (C. Deroulers, M.B.); Clinical Research Unit, Hôpital Tarnier, AP-HP, Paris, France (F.F.); UMR 1163, Institut Imagine, Paris, France (D.G., R.C., F.B., N.B.); University René Descartes, PRES Sorbonne Paris Cité, Paris, France (R.C., M.P., T.B., S.P., M.Z., C.S., F.B., P.V., N.B.); Department of Neuropathology, Centre Hospitalier Sainte Anne, Paris, France (M.P., P.V.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Institute, Villejuif, France (J.G., C. Dufour); CNRS, UMR 8203, Gustave Roussy Institute, University Paris-Sud, Villejuif, France (J.G., C. Dufour); and Department of Pediatric Neurosurgery, Hôpital Necker Enfants Malades, Paris, France (T.B., S.P., M.Z., C.S.).

Purpose To compare arterial spin labeling (ASL) data between low- and high-grade brain tumors in children to establish a cutoff to distinguish low- from high-grade neoplasms and to assess potential correlations between cerebral blood flow (CBF) and quantitative histologic microvascular data. Materials and Methods Approval was obtained from the regional review board. ASL data obtained in 129 children between 2011 and 2015 were retrospectively analyzed. CBF and relative CBF in the most perfused area of each neoplasm and contrast enhancement were quantified with a semiquantitative ratio. The correlation between CBF and microvascular density was analyzed in specimens stained with anti-CD34. Results were controlled in two validation cohorts with 1.5- and 3.0-T magnetic resonance (MR) imaging. Results Mean CBF was significantly higher for high-grade than for low-grade hemispheric (116 mL/min/100 g [interquartile range {IQR}, 73-131 mL/min/100 g] vs 29 mL/min/100 g [IQR, 23-35 29 mL/min/100 g], P < .001), thalamic (87 mL/min/100 g [IQR, 73-100 mL/min/100 g] vs 36 mL/min/100 g [IQR, 30-40 mL/min/100 g], P = .016), and posterior fossa (59 mL/min/100 g [IQR, 45-91 mL/min/100 g] vs 33 mL/min/100 g [IQR, 25-40 mL/min/100 g], P < .001) tumors. With a cutoff of 50 mL/min/100 g, sensitivity and specificity were 90% (95% confidence interval [CI]: 68, 100) and 93% (95% CI: 66, 100), respectively, for hemispheric tumors; 100% (95% CI: 48, 100) and 80% (95% CI: 28, 100), respectively, for thalamic tumors; and 65% (95% CI: 51, 78) and 94% (95% CI: 80, 99), respectively, for posterior fossa tumors. In posterior fossa tumors, additional use of the CBF-to-contrast enhancement ratio yielded sensitivity and specificity of 96% (95% CI: 87, 100) and 97% (95% CI: 84, 100), respectively. Use of a simple algorithm based on these values yielded an accuracy of 93% (95% CI: 87, 97). Validation sets yielded similar results, with grading accuracy of 88% (95% CI: 62, 98) with 1.5-T MR imaging and 77% (95% CI: 46, 95) with 3.0-T MR imaging. CBF was strongly correlated with microvascular density (R = 0.66, P < .001). Conclusion High-grade pediatric brain tumors display higher CBF than do low-grade tumors, and they may be accurately graded by using these values. CBF is correlated with tumor microvascular density. RSNA, 2016 Online supplemental material is available for this article.
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http://dx.doi.org/10.1148/radiol.2016152228DOI Listing
November 2016

Magnetic resonance imaging arterial-spin-labelling perfusion alterations in childhood migraine with atypical aura: a case-control study.

Dev Med Child Neurol 2016 09 6;58(9):965-9. Epub 2016 Apr 6.

Pediatric Radiology Department, Hôpital Necker - Enfants Malades, INSERM UMR1163 and U1000, Institut Imagine, Université Paris Descartes - Sorbonne Paris Cité, Paris, France.

Aim: Atypical migraine with aura can be challenging to diagnose. Arterial-spin-labelling (ASL) is able to non-invasively quantify brain perfusion. Our aim was to report cerebral blood flow (CBF) alterations using ASL, at the acute phase of atypical migraine with aura in children.

Method: Paediatric patients were retrospectively included if (1) referred for acute neurological deficit(s), (2) underwent brain magnetic resonance imaging (MRI) at presentation with ASL sequence, and (3) had subsequent diagnosis of migraine with aura. Neurological symptom-free controls were matched for age. Twenty-eight regions of interest (ROIs) were drawn on CBF maps for each participant/control.

Results: Ten patients were included (median age 13y, range 8-16y). Eight of 10 had multiple aura symptoms during the episode. For every patient, CBF was decreased in a brain region consistent with symptoms when MRI was performed less than 14 hours after onset (n=7 patients) and increased if the MRI was performed 17 hours or more after (n=4 MRIs).

Interpretation: MRI-ASL appears to be a promising tool for the diagnostic workup and differentials exclusion in paediatric migraine with aura. Constant and time-consistent non-territorial CBF modifications were found in our sample providing additional insight to migraine with aura pathophysiology. The authors encourage implementing this sequence at the acute phase of unexplained paediatric neurological deficits, with or without accompanying headache.
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http://dx.doi.org/10.1111/dmcn.13123DOI Listing
September 2016

Progressive paralyzing sciatica revealing a pelvic pseudoaneurysm a year after hip surgery in a 12yo boy.

Eur J Paediatr Neurol 2016 Jan 26;20(1):179-82. Epub 2015 Oct 26.

Department of Pediatric Radiology, Necker Enfants-Malades Hospital, Paris, France.

Identifying extra spinal causes of a lumbar radiculopathy or polyneuropathy can be a tricky diagnosis challenge, especially in children. Among them, traumatic or iatrogenic pseudoaneurysms of iliac arteries have been seldom reported, in adults' series. The authors report an unusual case of progressive paralyzing left sciatica and lumbar plexopathy in a 12 years old boy, 12 months after a pelvic osteotomy for bilateral hip luxation secondary to osteochondritis dissecans. Spine MRI and pelvic CT angiography revealed a giant internal iliac artery pseudoaneurysm, enclosed in a chronic hematoma. The patient was successfully treated with endovascular coil embolization, and subsequent surgical hematoma evacuation. However, three months after treatment, neurological recovery was incomplete. This case highlights the importance of a rapid and extensive diagnosis work up of all causes of lower limb radiculopathies in children, including pelvic arteries lesions especially after pelvic surgery to avoid therapeutic delays that may jeopardize the chances of neurological recovery.
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http://dx.doi.org/10.1016/j.ejpn.2015.10.004DOI Listing
January 2016

Lenalidomide-induced regenerative macronodules infarction in a cirrhosis patient.

Clin Res Hepatol Gastroenterol 2013 Apr 13;37(2):213-5. Epub 2013 Mar 13.

Service de radiologie, hôpital Saint-Antoine, groupe hospitalier Saint-Antoine, AP-HP, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France.

Hepatic regenerative macronodules observed in hepatic cirrhosis are sensitive to ischemia. Lenalidomide is a thalidomide analog used for the treatment of myelodysplastic syndromes, with pleiotropic activities including induction of apoptosis, inhibition of angiogenesis and broad immunomodulatory effects. It has been approved by the Food and Drug Administration (FDA) in the United States and by the European Medicines Agency (EMEA) in 2007 for the use in combination with dexamethasone in the treatment of relapsed or refractory multiple myeloma. We report a unique observation, which strongly suggests the role of Lenalidomide in hepatic regenerative macronodules infarction.
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http://dx.doi.org/10.1016/j.clinre.2013.01.007DOI Listing
April 2013