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1.
Clin Cancer Res ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924736

RESUMO

BACKGROUND: The HERBY trial evaluated the benefit of the addition of the antiangiogenic agent Bevacizumab (BEV) to radiotherapy/temozolomide (RT/TMZ) in pediatric patients with newly diagnosed non-brainstem high-grade glioma (HGG). The work presented here aims to correlate imaging characteristics and outcome measures with pathologic and molecular data. METHODS: Radiological, pathologic, and molecular data were correlated with trial clinical information to retrospectively re-evaluate event-free survival (EFS) and overall survival (OS). RESULTS: One-hundred thirteen patients were randomized to the RT/TMZ arm (n = 54) or the RT/TMZ+BEV (BEV arm; n = 59). The tumor arose in the cerebral hemispheres in 68 patients (Cerebral group) and a midline location in 45 cases (Midline group). Pathologic diagnosis was available in all cases and molecular data in 86 of 113. H3 K27M histone mutations were present in 23 of 32 Midline cases and H3 G34R/V mutations in 7 of 54 Cerebral cases. Total/near-total resection occurred in 44 of 68 (65%) Cerebral cases but in only 5 of 45 (11%) Midline cases (P < 0.05). Leptomeningeal metastases (27 cases, 13 with subependymal spread) at relapse were more frequent in Midline (17/45) than in Cerebral tumors (10/68, P < 0.05). Mean OS (14.1 months) and EFS (9.0 months) in Midline tumors were significantly lower than mean OS (20.7 months) and EFS (14.9 months) in Cerebral tumors (P < 0.05). Pseudoprogression occurred in 8 of 111 (6.2%) cases. CONCLUSIONS: This study has shown that the poor outcome of midline tumors (compared with cerebral) may be related to (1) lesser surgical resection, (2) H3 K27M histone mutations, and (3) higher leptomeningeal dissemination.

2.
Pediatr Blood Cancer ; 67(1): e28032, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31595663

RESUMO

AIM: To assess objective response after two cycles of temozolomide and topotecan (TOTEM) in children with refractory or relapsed miscellaneous extracranial solid and central nervous system (CNS) tumors, including medulloblastoma and primitive neuroectodermal tumors (PNET). PROCEDURE: Multicenter, nonrandomized, phase 2 basket trial including children with solid tumors, completed by a one-stage design confirmatory cohort for medulloblastoma, and an exploratory cohort for PNET. Main eligibility criteria were refractory/relapsed measurable disease and no more than two prior treatment lines. Temozolomide was administered orally at 150 mg/m2 /day followed by topotecan at 0.75 mg/m2 /day intravenously for five consecutive days every 28 days. Tumor response was assessed every two cycles according to WHO criteria and reviewed independently. RESULTS: Thirty-two patients were enrolled and treated in the miscellaneous solid tumor and 33 in the CNS strata; 20 patients with medulloblastoma and six with PNET were included in the expansion cohorts. The median age at inclusion was 10.0 years (range, 0.9-20.9). In the basket cohorts, confirmed complete and partial responses were observed in one glioma, four medulloblastoma, and one PNET, leading to the extension. The overall objective response rate (ORR) in medulloblastoma was 28% (95% CI, 12.7-47.2) with 1/29 complete and 7/29 partial responses, those for PNET 10% (95% CI, 0.3-44.5). Post hoc Bayesian analysis estimates that the true ORR in medulloblastoma is probably between 20% and 30% and below 20% in PNET. The most common treatment-related toxicities of the combination therapy were hematologic. CONCLUSIONS: Temozolomide-topotecan results in significant ORR in children with recurrent and refractory medulloblastoma with a favorable toxicity profile.

3.
Sci Rep ; 9(1): 9252, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31239453

RESUMO

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.

4.
Phys Med ; 49: 99-104, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29866350

RESUMO

OBJECTIVE: To demonstrate that the use of step-and-shoot (SAS) mode in paediatric cardiac CT angiography (CCTA) is possible at heart rates (HR) greater than 65 bpm, allowing low-dose acquisition with single-source 64-slices CT. METHODS: We retrospectively included 125 paediatric patients (0-6 years). CCTA was performed with SAS at diastolic phase in 31 patients (group D, HR < 65 bpm), at systolic phase in 45 patients (group S, HR ≥ 65 bpm) and with non-gated mode in 49 patients (group NG). Effective dose (ED) and image quality using a 3-grade scoring scale (1, excellent; 2, moderate; 3, insufficient) of group S were compared with group D for coronary examinations and group NG for entire thorax vascular anatomy. RESULTS: For coronary indications, median ED was 0.6 mSv in group D versus 0.9 mSv in group S (p < 0.01). For whole thorax indications, median ED was 2.7 mSv in group NG versus 1.1 mSv in group S (p < 0.001). The mean image quality score was (1.4 ±â€¯0.6) points in group D, (1.4 ±â€¯0.7) in group S for coronary indications (p = 0.9), (1.3 ±â€¯0.6) in group S for whole thorax indications and (2.0 ±â€¯0.0) in group NG (p < 0.001). CONCLUSION: SAS mode is feasible in children with HR greater than 65 bpm allowing low-dose CCTA. It provided comparable image quality in systole, compared to diastole. SAS at the systolic phase provided better image quality with less radiation dose compared to non-gated scans for whole thorax examinations.


Assuntos
Frequência Cardíaca , Coração/diagnóstico por imagem , Doses de Radiação , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Exposição à Radiação/análise , Radiografia Torácica/efeitos adversos , Tomografia Computadorizada por Raios X/efeitos adversos
5.
Phys Med Biol ; 63(10): 105003, 2018 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-29633962

RESUMO

Few methodological studies regarding widely used textural indices robustness in MRI have been reported. In this context, this study aims to propose some rules to compute reliable textural indices from multimodal 3D brain MRI. Diagnosis and post-biopsy MR scans including T1, post-contrast T1, T2 and FLAIR images from thirty children with diffuse intrinsic pontine glioma (DIPG) were considered. The hybrid white stripe method was adapted to standardize MR intensities. Sixty textural indices were then computed for each modality in different regions of interest (ROI), including tumor and white matter (WM). Three types of intensity binning were compared [Formula: see text]: constant bin width and relative bounds; [Formula: see text] constant number of bins and relative bounds; [Formula: see text] constant number of bins and absolute bounds. The impact of the volume of the region was also tested within the WM. First, the mean Hellinger distance between patient-based intensity distributions decreased by a factor greater than 10 in WM and greater than 2.5 in gray matter after standardization. Regarding the binning strategy, the ranking of patients was highly correlated for 188/240 features when comparing [Formula: see text] with [Formula: see text], but for only 20 when comparing [Formula: see text] with [Formula: see text], and nine when comparing [Formula: see text] with [Formula: see text]. Furthermore, when using [Formula: see text] or [Formula: see text] texture indices reflected tumor heterogeneity as assessed visually by experts. Last, 41 features presented statistically significant differences between contralateral WM regions when ROI size slightly varies across patients, and none when using ROI of the same size. For regions with similar size, 224 features were significantly different between WM and tumor. Valuable information from texture indices can be biased by methodological choices. Recommendations are to standardize intensities in MR brain volumes, to use intensity binning with constant bin width, and to define regions with the same volumes to get reliable textural indices.


Assuntos
Neoplasias do Tronco Encefálico/patologia , Glioma/patologia , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Substância Branca/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos
7.
Childs Nerv Syst ; 34(2): 359-362, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28921047

RESUMO

BACKGROUND: Brain dermoid cysts are very rare lesions. Although benign, these cysts may be associated with devastating complications due to mass effect or meningitis. The discovery of completely asymptomatic dermoid cysts in the pediatric population is exceedingly rare. Despite the advances in imaging modalities, it sometimes remains difficult to exclude the differential diagnosis of craniopharyngioma. CASE REPORT: We describe a 12-year-old boy addressed for suspicion of craniopharyngioma diagnosed by decreased visual acuity, bitemporal hemianopia and a CT scan showing a large hypodense suprasellar lesion with intralesional calcifications. Despite the unusual localization and size of this lesion, the absence of dermal sinus commonly found, and before visualizing a hyperintense mass on MRI-diffusion, the diagnosis of craniopharyngioma was ruled out in favor of a dermoid cyst. Radical excision was performed. CONCLUSION: In the suprasellar area, craniopharyngioma and dermoid cyst may have very similar radiological aspects: low density masses on CT scan and a hyperintense signal on T1-weighted MRI sequences with a variable signal on T2-weighted sequences. Hitherto, only two cases in literature have described suprasellar dermoid cyst. Their initial diagnosis was facilitated by the presence of a dermal sinus.


Assuntos
Craniofaringioma/diagnóstico por imagem , Cisto Dermoide/diagnóstico por imagem , Imagem por Ressonância Magnética , Neoplasias Hipofisárias/diagnóstico por imagem , Criança , Craniofaringioma/cirurgia , Cisto Dermoide/cirurgia , Diagnóstico Diferencial , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Neoplasias Hipofisárias/cirurgia
8.
Neuro Oncol ; 20(7): 994-1002, 2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29244086

RESUMO

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.


Assuntos
Neoplasias do Tronco Encefálico/patologia , Circulação Cerebrovascular , Glioma/patologia , Imagem Multimodal/métodos , Radioterapia/métodos , Adolescente , Neoplasias do Tronco Encefálico/irrigação sanguínea , Neoplasias do Tronco Encefálico/radioterapia , Estudos de Casos e Controles , Criança , Pré-Escolar , Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Feminino , Seguimentos , Glioma/irrigação sanguínea , Glioma/radioterapia , Humanos , Estudos Longitudinais , Masculino , Prognóstico , Curva ROC , Estudos Retrospectivos
9.
Brain ; 140(10): 2586-2596, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28969390

RESUMO

Dominant optic atrophy is a blinding disease due to the degeneration of the retinal ganglion cells, the axons of which form the optic nerves. In most cases, the disease is caused by mutations in OPA1, a gene encoding a mitochondrial large GTPase involved in cristae structure and mitochondrial network fusion. Using exome sequencing, we identified dominant mutations in DNM1L on chromosome 12p11.21 in three large families with isolated optic atrophy, including the two families that defined the OPA5 locus on chromosome 19q12.1-13.1, the existence of which is denied by the present study. Analyses of patient fibroblasts revealed physiological abundance and homo-polymerization of DNM1L, forming aggregates in the cytoplasm and on highly tubulated mitochondrial network, whereas neither structural difference of the peroxisome network, nor alteration of the respiratory machinery was noticed. Fluorescence microscopy of wild-type mouse retina disclosed a strong DNM1L expression in the ganglion cell layer and axons, and comparison between 3-month-old wild-type and Dnm1l+/- mice revealed increased mitochondrial length in retinal ganglion cell soma and axon, but no degeneration. Thus, our results disclose that in addition to OPA1, OPA3, MFN2, AFG3L2 and SPG7, dominant mutations in DNM1L jeopardize the integrity of the optic nerve, suggesting that alterations of the opposing forces governing mitochondrial fusion and fission, similarly affect retinal ganglion cell survival.


Assuntos
GTP Fosfo-Hidrolases/genética , Proteínas Associadas aos Microtúbulos/genética , Dinâmica Mitocondrial/genética , Proteínas Mitocondriais/genética , Mutação/genética , Atrofia Óptica/genética , Adolescente , Adulto , Animais , Células Cultivadas , Criança , Saúde da Família , Feminino , Fibroblastos/patologia , Fibroblastos/ultraestrutura , Humanos , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Consumo de Oxigênio/genética , Peroxissomos/patologia , Retina/patologia , Retina/ultraestrutura
10.
Int J Radiat Oncol Biol Phys ; 99(2): 476-485, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28871999

RESUMO

PURPOSE: To use multimodal magnetic resonance imaging (MRI) to quantify treatment-induced changes in the whole volume of diffuse infiltrating pontine gliomas and correlate them with progression-free survival (PFS). METHODS AND MATERIALS: This prospective study included 22 children aged 3.3 to 14.7 years (median, 5.9 years). Multimodal MRI was performed at 3 distinct time points: before treatment, the first week following radiation therapy (RT), and 2 months after RT. The imaging protocol included morphologic, multi b-value diffusion; arterial spin labeling; and dynamic susceptibility contrast-enhanced perfusion. Morphologic and multimodal data-lesion volume, diffusion coefficients, relative cerebral blood flow, and relative cerebral blood volume (rCBV)-were recorded at the 3 aforementioned time points. The Wilcoxon test was used to compare each individual parameter variation between time points, and its correlation with PFS was assessed by the Spearman test. RESULTS: Following RT, the tumors' solid component volume decreased by 40% (P<.001). Their median diffusion coefficients decreased by 20% to 40% (P<.001), while median relative cerebral blood flow increased by 60% to 80% (P<.001) and median rCBV increased by 70% (P<.001). PFS was positively correlated with rCBV measured immediately after RT (P=.003), and in patients whose rCBV was above the cutoff value of 2.46, the median PFS was 4.6 months longer (P=.001). These indexes tended to return to baseline 2 months after RT. Lesion volume before or after RT was not correlated with survival. CONCLUSIONS: Multimodal MRI provides useful information about diffuse infiltrating pontine gliomas' response to treatment; rCBV increases following RT, and higher values are correlated with better PFS. High rCBV values following RT should not be mistaken for progression and could be an indicator of response to therapy.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/radioterapia , Encéfalo/irrigação sanguínea , Glioma/diagnóstico por imagem , Glioma/radioterapia , Adolescente , Antineoplásicos/uso terapêutico , Encéfalo/efeitos da radiação , Neoplasias do Tronco Encefálico/irrigação sanguínea , Neoplasias do Tronco Encefálico/patologia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Meios de Contraste , Progressão da Doença , Intervalo Livre de Doença , Cloridrato de Erlotinib/administração & dosagem , Feminino , Glioma/irrigação sanguínea , Glioma/patologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Estudos Prospectivos , Sirolimo/administração & dosagem , Estatísticas não Paramétricas , Análise de Sobrevida , Fatores de Tempo , Carga Tumoral/efeitos da radiação
11.
Am J Med Genet A ; 173(6): 1521-1530, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28422438

RESUMO

Moyamoya syndrome (MMS) is the most common cerebral vasculopathy among children with neurofibromatosis type 1 (NF1). In this study, we clinically, radiologically, and genetically examined a cohort that was not previously described, comprising European children with NF1 and MMS. The NF1 genotyping had been registered. This study included 18 children. The mean age was 2.93 ± 3.03 years at the NF1 diagnosis and 7.43 ± 4.27 years at the MMS diagnosis. In seven patients, MMS was diagnosed before or at the same time as NF1. Neuroimaging was performed in 10 patients due to clinical symptoms, including headache (n = 6), cerebral infarction (n = 2), and complex partial seizures (n = 2). The remaining eight children (47%) had MMS diagnosed incidentally. Sixteen children were characterized molecularly. The features of MMS were similar between patients with and without NF1. Additionally, the NF1 phenotype and genotype were similar between children with and without MMS. Interestingly, three children experienced tumors with malignant histology or behavior. The presence of two first cousins in our cohort suggested that there may be potential genetic factors, not linked to NF1, with an additional role respect of NF1 might play a role in MMS pathogenesis. The incidental diagnosis of MMS, and the observation that, among children with NF1, those with MMS were clinically indistinguishable from those without MMS, suggested that it might be worthwhile to add an angiographic sequence to brain MRIs requested for children with NF1. A MMS diagnosis may assist in properly addressing an NF1 diagnosis in very young children who do not fulfill diagnostic criteria.


Assuntos
Imagem por Ressonância Magnética , Doença de Moyamoya/genética , Neurofibromatose 1/genética , Neurofibromina 1/genética , Adolescente , Sequência de Bases , Criança , Pré-Escolar , Feminino , França , Genótipo , Humanos , Lactente , Recém-Nascido , Itália , Masculino , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/fisiopatologia , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico por imagem , Neurofibromatose 1/fisiopatologia , Neuroimagem/métodos
12.
J Neurooncol ; 132(2): 255-266, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28110411

RESUMO

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6-6.4 months) and the median overall survival is 11.0 months (95% CI 10.5-11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico por imagem , Glioma/diagnóstico por imagem , Serviços de Informação , Cooperação Internacional , Imagem por Ressonância Magnética , Sistema de Registros , Criança , Pré-Escolar , Europa (Continente) , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Ponte/diagnóstico por imagem , Adulto Jovem
13.
Radiology ; 281(2): 553-566, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27257950

RESUMO

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.


Assuntos
Neoplasias Encefálicas/patologia , Angiografia por Ressonância Magnética/métodos , Marcadores de Spin , Adolescente , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/terapia , Circulação Cerebrovascular , Criança , Pré-Escolar , Meios de Contraste , Feminino , Humanos , Lactente , Masculino , Gradação de Tumores , Estudos Retrospectivos , Sensibilidade e Especificidade
15.
Dev Med Child Neurol ; 58(9): 965-9, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27060350

RESUMO

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.


Assuntos
Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Imagem por Ressonância Magnética/métodos , Enxaqueca com Aura/diagnóstico por imagem , Enxaqueca com Aura/fisiopatologia , Adolescente , Encéfalo/irrigação sanguínea , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Perfusão , Estudos Retrospectivos , Marcadores de Spin
16.
Am J Hum Genet ; 98(5): 971-980, 2016 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-27108797

RESUMO

Gillespie syndrome (GS) is a rare variant form of aniridia characterized by non-progressive cerebellar ataxia, intellectual disability, and iris hypoplasia. Unlike the more common dominant and sporadic forms of aniridia, there has been no significant association with PAX6 mutations in individuals with GS and the mode of inheritance of the disease had long been regarded as uncertain. Using a combination of trio-based whole-exome sequencing and Sanger sequencing in five simplex GS-affected families, we found homozygous or compound heterozygous truncating mutations (c.4672C>T [p.Gln1558(∗)], c.2182C>T [p.Arg728(∗)], c.6366+3A>T [p.Gly2102Valfs5(∗)], and c.6664+5G>T [p.Ala2221Valfs23(∗)]) and de novo heterozygous mutations (c.7687_7689del [p.Lys2563del] and c.7659T>G [p.Phe2553Leu]) in the inositol 1,4,5-trisphosphate receptor type 1 gene (ITPR1). ITPR1 encodes one of the three members of the IP3-receptors family that form Ca(2+) release channels localized predominantly in membranes of endoplasmic reticulum Ca(2+) stores. The truncation mutants, which encompass the IP3-binding domain and varying lengths of the modulatory domain, did not form functional channels when produced in a heterologous cell system. Furthermore, ITPR1 p.Lys2563del mutant did not form IP3-induced Ca(2+) channels but exerted a negative effect when co-produced with wild-type ITPR1 channel activity. In total, these results demonstrate biallelic and monoallelic ITPR1 mutations as the underlying genetic defects for Gillespie syndrome, further extending the spectrum of ITPR1-related diseases.


Assuntos
Aniridia/etiologia , Ataxia Cerebelar/etiologia , Genes Dominantes/genética , Genes Recessivos/genética , Receptores de Inositol 1,4,5-Trifosfato/genética , Deficiência Intelectual/etiologia , Mutação/genética , Adolescente , Aniridia/patologia , Ataxia Cerebelar/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/patologia , Masculino , Linhagem
17.
Cereb Cortex ; 26(6): 2823-31, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26946130

RESUMO

Processing eye-gaze information is a key step to human social interaction. Neuroimaging studies have shown that superior temporal sulcus (STS) is highly implicated in eye-gaze perception. In autism, a lack of preference for the eyes, as well as anatomo-functional abnormalities within the STS, has been described. To date, there are no experimental data in humans showing whether it is possible to interfere with eye-gaze processing by modulating STS neural activity. Here, we measured eye-gaze perception before and after inhibitory transcranial magnetic stimulation (TMS) applied over the posterior STS (pSTS) in young healthy volunteers. Eye-gaze processing, namely overt orienting toward the eyes, was measured using eye tracking during passive visualization of social movies. Inhibition of the right pSTS led participants to look less to the eyes of characters during visualization of social movies. Such effect was specific for the eyes and was not observed after inhibition of the left pSTS nor after placebo TMS. These results indicate for the first time that interfering with the right pSTS neural activity transitorily disrupts the behavior of orienting toward the eyes and thus indirectly gaze perception, a fundamental process for human social cognition. These results could open up new perspectives in therapeutic interventions in autism.


Assuntos
Fixação Ocular , Percepção Social , Lobo Temporal/fisiologia , Percepção Visual/fisiologia , Cognição/fisiologia , Medições dos Movimentos Oculares , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Inibição Neural , Lobo Temporal/diagnóstico por imagem , Estimulação Magnética Transcraniana , Adulto Jovem
18.
Eur Radiol ; 26(7): 2030-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26433957

RESUMO

OBJECTIVES: To assess the impact of different protocols on radiation dose and image quality for paediatric coronary computed tomography (cCT). MATERIALS AND METHODS: From January-2012 to June-2014, 140 children who underwent cCT on a 64-slice scanner were included. Two consecutive changes in imaging protocols were performed: 1) the use of adaptive statistical iterative reconstruction (ASIR); 2) the optimization of acquisition parameters. Effective dose (ED) was calculated by conversion of the dose-length product. Image quality was assessed as excellent, good or with significant artefacts. RESULTS: Patients were divided in three age groups: 0-4, 5-7 and 8-18 years. The use of ASIR combined to the adjustment of scan settings allowed a reduction in the median ED of 58 %, 82 % and 85 % in 0-4, 5-7 and 8-18 years group, respectively (7.3 ± 1.4 vs 3.1 ± 0.7 mSv, 5.5 ± 1.6 vs 1 ± 1.9 mSv and 5.3 ± 5.0 vs 0.8 ± 2.0 mSv, all p < 0,05). Prospective protocol was used in 51 % of children. The reduction in radiation dose was not associated with reduction in diagnostic image quality as assessed by the frequency of coronary segments with excellent or good image quality (88 %). CONCLUSIONS: cCT can be obtained at very low radiation doses in children using ASIR, and prospective acquisition with optimized imaging parameters. KEY POINTS: • Using ASIR allows 25 % to 41 % reduction in the ED. • Prospective protocol is used up to 51 % of children after premedication. • Low dose is possible using ASIR and optimized prospective paediatric cCT.


Assuntos
Cardiopatias/diagnóstico por imagem , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Artefatos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Tomografia Computadorizada por Raios X/normas
19.
Acta Neuropathol ; 130(6): 815-27, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26399631

RESUMO

Diffuse intrinsic pontine glioma (DIPG) is the most severe paediatric solid tumour, with no significant therapeutic progress made in the past 50 years. Recent studies suggest that diffuse midline glioma, H3-K27M mutant, may comprise more than one biological entity. The aim of the study was to determine the clinical and biological variables that most impact their prognosis. Ninety-one patients with classically defined DIPG underwent a systematic stereotactic biopsy and were included in this observational retrospective study. Histone H3 genes mutations were assessed by immunochemistry and direct sequencing, whilst global gene expression profiling and chromosomal imbalances were determined by microarrays. A full description of the MRI findings at diagnosis and at relapse was integrated with the molecular profiling data and clinical outcome. All DIPG but one were found to harbour either a somatic H3-K27M mutation and/or loss of H3K27 trimethylation. We also discovered a novel K27M mutation in HIST2H3C, and a lysine-to-isoleucine substitution (K27I) in H3F3A, also creating a loss of trimethylation. Patients with tumours harbouring a K27M mutation in H3.3 (H3F3A) did not respond clinically to radiotherapy as well, relapsed significantly earlier and exhibited more metastatic recurrences than those in H3.1 (HIST1H3B/C). H3.3-K27M-mutated DIPG have a proneural/oligodendroglial phenotype and a pro-metastatic gene expression signature with PDGFRA activation, while H3.1-K27M-mutated tumours exhibit a mesenchymal/astrocytic phenotype and a pro-angiogenic/hypoxic signature supported by expression profiling and radiological findings. H3K27 alterations appear as the founding event in DIPG and the mutations in the two main histone H3 variants drive two distinct oncogenic programmes with potential specific therapeutic targets.


Assuntos
Neoplasias do Tronco Encefálico/genética , Glioma/genética , Histonas/genética , Mutação , Astrócitos/metabolismo , Astrócitos/patologia , Astrócitos/efeitos da radiação , Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/radioterapia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Glioma/diagnóstico , Glioma/patologia , Glioma/radioterapia , Células HeLa , Humanos , Masculino , Neurônios/metabolismo , Neurônios/patologia , Neurônios/efeitos da radiação , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Oligodendroglia/efeitos da radiação , Fenótipo , Ponte/metabolismo , Ponte/patologia , Ponte/efeitos da radiação , Ponte/cirurgia , Prognóstico
20.
Rev Prat ; 62(10): 1391-4, 2012 Dec.
Artigo em Francês | MEDLINE | ID: mdl-23424919

RESUMO

Cerebral imaging studies are performed systematically in children with non-idiopathic epilepsy. Magnetic resonance imaging (MRI) of the brain is the preferred technique. In emergency settings, when immediate neurosurgical treatment may be required (acute haemorrhage, etc.) non-enhanced computed tomography (NECT) is indicated, due to the shorter exam duration and the greater availability. Despite a normal NECT scan, the MRI scan is always indicated for non-idiopathic epileptic patients to search for small cortical sub-cortical abnormalities often overlooked in CT scans. On the other hand, a second intention CT scan to look for calcification may be indicated when tuberous sclerosis, Aicardi-Goutieres syndrome, infectious foetal diseases are suspected. The MRI protocol is adapted to each case based on clinical and EEG findings, but will always include a T1 weighted-3-dimensional (isotropic) acquisition, axial and coronal T2 and T2-Flair weighted images and T2*. Contrast injection is mandatory especially when abnormal findings are seen on the MRI precontrast images.


Assuntos
Encéfalo/diagnóstico por imagem , Neuroimagem/métodos , Idade de Início , Encéfalo/patologia , Criança , Humanos , Imagem por Ressonância Magnética , Convulsões/diagnóstico por imagem , Convulsões/epidemiologia , Convulsões/patologia , Tomografia Computadorizada por Raios X
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