Molecular and clinicopathologic characteristics of CNS embryonal tumors with BRD4::LEUTX fusion.

Central nervous system (CNS) embryonal tumors are a heterogeneous group of high-grade malignancies, and the increasing clinical use of methylation profiling and next-generation sequencing has led to the identification of molecularly distinct subtypes. One proposed tumor type, CNS tumor with BRD4::LEUTX fusion, has been described. As only a few CNS tumors with BRD4::LEUTX fusions have been described, we herein characterize a cohort of 9 such cases (4 new, 5 previously published) to further describe their clinicopathologic and molecular features. We demonstrate that CNS embryonal tumor with BRD4::LEUTX fusion comprises a well-defined methylation class/cluster. We find that patients are young (4 years or younger), with large tumors at variable locations, and frequently with evidence of leptomeningeal/cerebrospinal fluid (CSF) dissemination. Histologically, tumors were highly cellular with high-grade embryonal features. Immunohistochemically, 5/5 cases showed synaptophysin and 4/5 showed OLIG2 expression, thus overlapping with CNS neuroblastoma, FOXR2-activated. DNA copy number profiles were generally flat; however, two tumors had chromosome 1q gains. No recurring genomic changes, besides the presence of the fusion, were found. The LEUTX portion of the fusion transcript was constant in all cases assessed, while the BRD4 portion varied but included a domain with proto-oncogenic activity in all cases. Two patients with clinical follow up available had tumors with excellent response to chemotherapy. Two of our patients were alive without evidence of recurrence or progression after gross total resection and chemotherapy at 16 and 33 months. One patient relapsed, and the last of our four patients died of disease one month after diagnosis. Overall, this case series provides additional evidence for this as a distinct tumor type defined by the presence of a specific fusion as well as a distinct DNA methylation signature. Studies on larger series are required to further characterize these tumors.

Narrative impairment, white matter damage and CSF biomarkers in the Alzheimer's disease spectrum.

BACKGROUND: Narrative discourse (ND) refers to one's ability to verbally reproduce a sequence of temporally and logically-linked events. Impairments in ND may occur in subjects with Amnestic Mild Cognitive Impairment (aMCI) and Alzheimer's Disease (AD), but correlates across this function, neuroimaging and cerebrospinal fluid (CSF) AD biomarkers remain understudied. OBJECTIVES: We sought to measure correlates among ND, Diffusion Tensor Imaging (DTI) indexes and AD CSF biomarkers in patients within the AD spectrum. RESULTS: Groups differed in narrative production (NProd) and comprehension. aMCI and AD presented poorer inference abilities than controls. AD subjects were more impaired than controls and aMCI regarding WB (p<0.01). ROIs DTI assessment distinguished the three groups. Mean Diffusivity (MD) in the uncinate, bilateral parahippocampal cingulate and left inferior occipitofrontal fasciculi negatively correlated with NProd. Changes in specific tracts correlated with T-tau/Aß1-42 ratio in CSF. CONCLUSIONS: AD and aMCI patients presented more ND impairments than controls. Those findings were associated with changes in ventral language-associated and in the inferior parahippocampal pathways. The latest were correlated with biomarkers' levels in the CSF. METHODS: AD (N=14), aMCI (N=31) and Control (N=39) groups were compared for whole brain (WB) and regions of interest (ROI) DTI parameters, ND and AD CSF biomarkers.

Inter-method and anatomical correlates of episodic memory tests in the Alzheimer's Disease spectrum.

BACKGROUND: Episodic memory impairments have been described as initial clinical findings in the Alzheimer's Disease (AD) spectrum, which could be associated with the presence of early hippocampal dysfunction. However, correlates between performances in neuropsychological tests and hippocampal volumes in AD were inconclusive in the literature. Divergent methods to assess episodic memory have been depicted as a major source of heterogeneity across studies. METHODS: We examined correlates among performances in three different delayed-recall tasks (Rey-Auditory Verbal-Learning Test-RAVLT, Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale) and fully-automated volumetric measurements of the hippocampus (estimated using Neuroquant®) of 83 older subjects (47 controls, 27 Mild Cognitive Impairment individuals and 9 participants with Dementia due to AD). RESULTS: Inter-method correlations of episodic memory performances were at most moderate. Scores in the RAVLT predicted up to 48% of variance in HOC (Hippocampal Occupancy Score) among subjects in the AD spectrum. DISCUSSION: Tests using different stimuli (verbal or visual) and presenting distinct designs (word list, story or figure learning) may assess divergent aspects in episodic memory, with heterogeneous anatomical correlates. CONCLUSIONS: Different episodic memory tests might not assess the same construct and should not be used interchangeably. Scores in RAVLT may correlate with the presence of neurodegeneration in AD.

Imaging findings in congenital Zika virus infection syndrome: an update.

BACKGROUND: Zika virus (ZIKV) is a neurotropic and neurotoxic RNA Flavivirus prompt to cause severe fetal brain dysmorphisms during pregnancy, a period of rapid and critical central nervous system development. A wide range of clinico-radiological findings of congenital ZIKV infections were reported in the literature, such as microcephaly, overlapping sutures, cortical migrational and corpus callosum abnormalities, intracranial calcifications, ventriculomegaly, brain stem and cerebellar malformations, spinal cord involvement, and joint contractures. ZIKV is also related to other severe neurological manifestations in grown-up individuals such as Guillain-Barré syndrome and encephalomyelitis. PURPOSE: Our purpose is to review the radiological central nervous system abnormalities of congenital ZIKV infection syndrome on different imaging modalities.

Comparison of human brain metabolite levels using 1H MRS at 1.5T and 3.0T.

Proton magnetic resonance spectroscopy (MRS) of the human brain has proven to be a useful technique in several neurological and psychiatric disorders and benefits from higher field scanners as signal intensity and spectral resolution are proportional to the magnetic field strength. OBJECTIVE: To investigate the effects of the magnetic field on the measurement of brain metabolites in a typical routine clinical setting. METHODS: Single voxel spectra were acquired from the posterior cingulate cortex in 26 healthy subjects. Each subject was scanned consecutively at 1.5T and 3.0T in a randomly distributed order. RESULTS: SNR and peak width improvements were observed at higher fields. However, SNR improvement was lower than the theoretical two-fold improvement. Other than the values obtained for creatine (Cre) and myo-Inositol (mI), which were both higher at 3.0T, all metabolite concentrations obtained were roughly the same at both field strengths. All the metabolite concentrations were estimated with a Cramer Rao lower bounds (CRLB) lower than 15% of the calculated concentrations. CONCLUSIONS: Even though the present study supports the expected benefits of higher field strength for MRS, there are several factors that can lead to different quantitative results when comparing 1.5T to 3.0T MRS. Future comparative studies are necessary to refine the metabolite thresholds for early detection and quantification of distinct neurological and psychiatric disorders using 3.0T MRS.

Espectroscopia de prótons por ressonância magnética (MRS) tem se mostrado uma técnica bastante útil em diversas doenças neurológicas e psiquiátricas. A utilização de sistemas de mais alto campo magnético favorece essa técnica uma vez que a intensidade do sinal e a resolução espectral são proporcionais à intensidade do campo. OBJETIVO: Avaliar o efeito do campo magnético sobre a medida dos níveis dos metabólitos cerebrais em uma típica rotina clínica. MÉTODOS: Os dados foram obtidos em 26 indivíduos saudáveis nos sistemas de 1.5T e 3.0T. As aquisições foram feitas sequencialmente e a ordem foi distribuida randomicamente. RESULTADOS: Foram observadas melhoras na relação sinal-ruído (SNR) e na largura de linha dos picos nos dados obtidos em campo maior. No entanto, a melhoria na SNR foi menor que o esperado teoricamente que seria o dobro da obtida em 1.5T. Exceto pelos valores obtidos para creatina e mio-inositol, que foram maiores em 3.0T, todas as concentrações de metabólitos obtidas foram aproximadamente a mesmo em ambos os campos. Todas as concentrações de metabólitos foram estimadas com Cramer Rao lower bounds (CRLB) inferior a 15% das concentrações calculadas. CONCLUSÕES: Apesar de o presente estudo dar suporte aos benefícios gerados pelo aumento do campo para a técnica de MRS, existem fatores que podem levar a diferentes resultados quantitativos quando se compara espectroscopia em 1.5T e 3.0T. Estudos comparativos serão necessários para refinar os limiares dos níveis de metabólitos para melhorar a acurácia da detecção de doenças neurológicas utilizando espectroscopia em 3.0T.

The human pyramidal syndrome Redux.

Experimental studies in nonhuman primates have questioned the selectivity of pyramidal tract damage in giving rise to the classical pyramidal syndrome in humans, characterized by permanent spastic hemiplegia (PSH). According to this view, concomitant injury of extrapyramidal pathways is necessary for the development of both hemiplegia and spasticity. In this study we used conventional magnetic resonance imaging and diffusion tensor imaging tractography to characterize the anatomical correlates of PSH in a patient with a rare and discrete unilateral lesion of the medullary pyramid. Our findings support the hypothesis that damage confined to the medullary pyramid/pyramidal tract is sufficient to produce PSH. In contrast to nonhuman primates, the human 'pyramidal' and 'pyramid' syndromes are equivalent clinico-anatomic concepts.