The Occipital Emissary Vein: A Possible Marker for Pseudotumor Cerebri

BACKGROUND AND PURPOSE: Transverse sinus stenosis can lead to pseudotumor cerebri syndrome by elevating the cerebral venous pressure. The occipital emissary vein is an inconstant emissary vein that connects the torcular herophili with the suboccipital veins of the external vertebral plexus. This retrospective study compares the prevalence and size of the occipital emissary vein in patients with pseudotumor cerebri syndrome with those in healthy control subjects to determine whether the occipital emissary vein could represent a marker of pseudotumor cerebri syndrome. MATERIALS AND METHODS: The cranial venous system of 46 adult patients with pseudotumor cerebri syndrome (group 1) was studied on CT venography images and compared with a group of 92 consecutive adult patients without pseudotumor cerebri syndrome who underwent venous assessment with gadolinium-enhanced 3D-T1 MPRAGE sequences (group 2). The presence of an occipital emissary vein was assessed, and its proximal (intraosseous) and distal (extracranial) maximum diameters were measured and compared between the 2 groups. Seventeen patients who underwent transverse sinus stent placement had their occipital emissary vein diameters measured before and after stent placement. RESULTS: Thirty of 46 (65%) patients in group 1 versus 29/92 (31.5%) patients in group 2 had an occipital emissary vein (P < .001). The average proximal and distal occipital emissary vein maximum diameters were significantly larger in group 1 (2.3 versus 1.6 mm, P <.005 and 3.3 versus 2.3 mm, P<.001). The average maximum diameters of the occipital emissary vein for patients who underwent transverse sinus stent placement were larger before stent placement than after stent placement: 2.6 versus 1.8 mm proximally (P<.06) and 3.7 versus 2.6 mm distally (P<.005). CONCLUSIONS: Occipital emissary veins are more frequent and larger in patients with pseudotumor cerebri syndrome than in healthy subjects, a finding consistent with their role as collateral venous pathway in transverse sinus stenosis. A prominent occipital emissary vein is an imaging sign that should raise the suspicion of pseudotumor cerebri syndrome.Fil: Hedjoudje, A.. Hospital Center University De Rouen; FranciaFil: Piveteau, A.. University Hospital of Geneva; SuizaFil: Gonzalez Campo, Cecilia. Sion Hospital; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencias Cognitivas y Traslacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Moghekar, A.. The Johns Hopkins Hospital; Estados UnidosFil: Gailloud, P.. The Johns Hopkins Hospital; Estados UnidosFil: San Millán, D.. Sion Hospital; Suiz

Reinspection of a Clinical Proteomics Tumor Analysis Consortium (CPTAC) Dataset with Cloud Computing Reveals Abundant Post-Translational Modifications and Protein Sequence Variants.

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has provided some of the most in-depth analyses of the phenotypes of human tumors ever constructed. Today, the majority of proteomic data analysis is still performed using software housed on desktop computers which limits the number of sequence variants and post-translational modifications that can be considered. The original CPTAC studies limited the search for PTMs to only samples that were chemically enriched for those modified peptides. Similarly, the only sequence variants considered were those with strong evidence at the exon or transcript level. In this multi-institutional collaborative reanalysis, we utilized unbiased protein databases containing millions of human sequence variants in conjunction with hundreds of common post-translational modifications. Using these tools, we identified tens of thousands of high-confidence PTMs and sequence variants. We identified 4132 phosphorylated peptides in nonenriched samples, 93% of which were confirmed in the samples which were chemically enriched for phosphopeptides. In addition, our results also cover 90% of the high-confidence variants reported by the original proteogenomics study, without the need for sample specific next-generation sequencing. Finally, we report fivefold more somatic and germline variants that have an independent evidence at the peptide level, including mutations in ERRB2 and BCAS1. In this reanalysis of CPTAC proteomic data with cloud computing, we present an openly available and searchable web resource of the highest-coverage proteomic profiling of human tumors described to date

Non-contrast MR imaging of blood-brain barrier permeability to water

Neuro Imaging Researc

Genome-wide, high-content siRNA screening identifies the Alzheimer's genetic risk factor FERMT2 as a major modulator of APP metabolism

Genome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer’s disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the “post-GWAS” era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective. We therefore developed a genome-wide, high-content siRNA screening approach and used it to assess the functional impact of gene under-expression on APP metabolism. We found that 832 genes modulated APP metabolism. Eight of these genes were located within AD susceptibility loci. Only FERMT2 (a β3-integrin co-activator) was also significantly associated with a variation in cerebrospinal fluid Aβ peptide levels in 2886 AD cases. Lastly, we showed that the under-expression of FERMT2 increases Aβ peptide production by raising levels of mature APP at the cell surface and facilitating its recycling. Taken as a whole, our data suggest that FERMT2 modulates the AD risk by regulating APP metabolism and Aβ peptide production

Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects

In a large multicentre study, Toledo et al. examine core Alzheimer's disease CSF biomarkers in 1233 cognitively normal subjects aged 40-85 years. Alzheimer disease-like changes in Aβ1-42 are seen as early as middle age, while APOE genotype strongly modifies age-related effects on both Aβ1-42 and phosphorylated/total ta

Genome-wide association study identifies four novel loci associated with Alzheimer's endophenotypes and disease modifiers

More than 20 genetic loci have been associated with risk for Alzheimer's disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case-control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ42), tau, and phosphorylated tau (ptau181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ42 near GLIS1 on 1p32.3 (β = -0.059, P = 2.08 × 10-8) and within SERPINB1 on 6p25 (β = -0.025, P = 1.72 × 10-8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10-2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10-2), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10-3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform future AD studies

Genome-wide association study identifies four novel loci associated with Alzheimer's endophenotypes and disease modifiers

More than 20 genetic loci have been associated with risk for Alzheimer’s disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case–control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ42), tau, and phosphorylated tau (ptau181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ42 near GLIS1 on 1p32.3 (β = −0.059, P = 2.08 × 10−8) and within SERPINB1 on 6p25 (β = −0.025, P = 1.72 × 10−8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10−2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10−2), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10−3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform future AD studies