Normal Pressure Hydrocephalus
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ABSTRACT:
PROVIDER: PRJNA679985 | ENA |
REPOSITORIES: ENA
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Project description:Cerebrospinal fluid transcripts may predict shunt surgery responses in normal pressure hydrocephalus
| PRJNA874691 | ENA
Project description:Molecular biomarkers for neurodegenerative diseases are critical for advancing diagnosis and therapy. Normal pressure hydrocephalus (NPH) is a neurological disorder characterized by progressive neurodegeneration, gait impairment, urinary incontinence and cognitive decline. In contrast to most other neurodegenerative disorders, NPH symptoms can be improved by the placement of a ventricular shunt that drains excess CSF. A major challenge in NPH management is the identification of patients who benefit from shunt surgery. Here, we perform genome-wide RNA sequencing of extracellular vesicles in CSF of 42 NPH patients, and we identify genes and pathways whose expression levels correlate with gait, urinary or cognitive symptom improvement after shunt surgery. We describe a machine learning algorithm trained on these gene expression profiles to predict shunt surgery response with high accuracy. The transcriptomic signatures we identified may have important implications for improving NPH diagnosis and treatment and for understanding disease aetiology.
2023-06-02 | GSE212236 | GEO
Project description:Though congenital hydrocephalus is heritable, it has been linked only to eight genes, one of which is MPDZ. Humans and mice that carry a truncated version of MPDZ incur severe hydrocephalus resulting in acute morbidity and lethality. We show by magnetic resonance imaging that contrast-medium penetrates into the brain ventricles of mice carrying a Mpdz loss-of-function mutation, whereas none is detected in the ventricles of normal mice, implying that the permeability of the choroid plexus epithelial cell monolayer is abnormally high. Comparative proteomic analysis of the cerebrospinal fluid of normal and hydrocephalic mice revealed up to a 53-fold increase in protein concentration, suggesting that transcytosis through the choroid plexus epithelial cells of Mpdz KO mice is substantially higher than in normal mice. These conclusions are supported by ultrastructural evidence, and by immunohistochemistry and cytology data. Our results provide a straightforward and concise explanation for the pathophysiology of Mpdz-linked hydrocephalus.
2018-11-23 | PXD011535 | Pride
Project description:Transcriptional profiling of the parietal cortex was performed in postnatal day 22 rats with obstructive hydrocephalus. An intracisternal injection of kaolin was done on postnatal day one, and severe hydrocephalus developed over 3 weeks. Hydrocephalic animals were compared to age-matched saline controls. The goal was to determine the effects of kaolin-induced neonatal hydrocephalus on gene expression. Two-condition experiment: kaolin-induced vs. saline-injected controls. Replicates: 5 treatment samples and 5 saline controls.
2010-07-30 | E-GEOD-16985 | biostudies-arrayexpress
Project description:Transcriptional profiling of the parietal cortex was performed in postnatal day 22 rats with obstructive hydrocephalus. An intracisternal injection of kaolin was done on postnatal day one, and severe hydrocephalus developed over 3 weeks. Hydrocephalic animals were compared to age-matched saline controls. The goal was to determine the effects of kaolin-induced neonatal hydrocephalus on gene expression.
2010-07-01 | GSE16985 | GEO
Project description:ObjectivesThe aim of this study was to determine the prevalence of idiopathic normal-pressure hydrocephalus (iNPH) in elderly persons in a large population-based sample using radiologic and clinical examinations.MethodsWe examined representative elderly populations aged 70 years and older that had undergone neuropsychiatric evaluations and CT of the brain between 1986 and 2000 (n = 1,238). Gait was evaluated by clinical examination and history of walking difficulty. Cognitive function was evaluated with the Mini-Mental State Examination and urinary incontinence by self-report. iNPH was diagnosed in concordance with the American-European iNPH guidelines. Exclusion criteria were history of meningitis, severe head trauma, and subarachnoid hemorrhage.ResultsThe prevalence of probable iNPH was 0.2% in those aged 70-79 years (n = 2) and 5.9% (n = 24) in those aged 80 years and older, with no difference between men and women. Only 2 of these persons had been treated for iNPH. Hydrocephalic ventricular enlargement, i.e., a CT image consistent with NPH, was found in 56 persons (4.5%). An Evans Index >0.3 was found in 256 (20.7%) and occluded sulci at the high convexity in 67 persons (5.4%). All of these findings were more common in the older age groups.ConclusionsMany elderly possess clinical and imaging features of iNPH, especially those older than 80 years. The number of persons with iNPH is probably much higher than the number of persons currently treated.
| S-EPMC4001197 | biostudies-literature
Project description:The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer's disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71.3 ± 8.1 years, three female and 12 male) and eight reference subjects (mean age 41.1 + 13.0 years, six female and two male) with suspected cerebrospinal fluid leakage (seven) and intracranial cyst (one). The imaging protocol included T1-weighted magnetic resonance imaging with equal sequence parameters before and at multiple time points through 24 h after intrathecal injection of the contrast agent gadobutrol at the lumbar level. All study subjects were kept in the supine position between examinations during the first day. Gadobutrol enhancement was measured at all imaging time points from regions of interest placed at predefined locations in brain parenchyma, the subarachnoid and intraventricular space, and inside the sagittal sinus. Parameters demonstrating gadobutrol enhancement and clearance in different locations were compared between idiopathic normal pressure hydrocephalus and reference subjects. A characteristic flow pattern in idiopathic normal hydrocephalus was ventricular reflux of gadobutrol from the subarachnoid space followed by transependymal gadobutrol migration. At the brain surfaces, gadobutrol propagated antegradely along large leptomeningeal arteries in all study subjects, and preceded glymphatic enhancement in adjacent brain tissue, indicating a pivotal role of intracranial pulsations for glymphatic function. In idiopathic normal pressure hydrocephalus, we found delayed enhancement (P < 0.05) and decreased clearance of gadobutrol (P < 0.05) at the Sylvian fissure. Parenchymal (glymphatic) enhancement peaked overnight in both study groups, possibly indicating a crucial role of sleep, and was larger in normal pressure hydrocephalus patients (P < 0.05 at inferior frontal gyrus). We interpret decreased gadobutrol clearance from the subarachnoid space, along with persisting enhancement in brain parenchyma, as signs of reduced glymphatic clearance in idiopathic normal hydrocephalus, and hypothesize that reduced glymphatic function is instrumental for dementia in this disease. The study shows promise for glymphatic magnetic resonance imaging as a method to assess human brain metabolic function and renders a potential for contrast enhanced brain extravascular space imaging.
| S-EPMC5841149 | biostudies-literature
Project description:To explore the genetic cause of a Chinese woman with fetal hydrocephalus X-linked hydrocephalus (XLH), a genetic disorder, has an incidence of 1/30,000 male births. The great proportion of XLH is ascribed to loss of function mutations of L1 cell adhesion molecule gene (L1CAM), but silent mutations in L1CAM with pathogenic potential were rare, and were usually ignored especially in WES detection. In the present study, we describe a novel silent L1CAM mutation in a Chinese pregnant woman reporting continuous five times pregnancies with fetal hydrocephalus. After fetal blood sampling, we found c.453G>T (p.Gly151=) in L1CAM gene of the fetus by whole exome sequencing (WES), RT-PCR of the mRNA from cord blood mononuclear cells and subsequent sequence analysis identified the mutation created a potential 5' splice site consensus sequence, which would result in an in-frame deletion of 72 bp from exon 5 and 24 amino acids of the L1CAM protein. Heterozygous mutations were confirmed in analyzing DNA and mRNA from peripheral blood mononuclear cells of the woman, and, a severe L1 syndrome was confirmed by fetal ultrasound scan and MRI. Our study first indicated c.453G>T (p.Gly151=) in L1CAM could be disease causing for hydrocephalus, which would aid in genetic counseling for the prenatal diagnosis of hydrocephalus. Meanwhile, it suggested some silent mutations detected in WES should not be ignored, splicing predictions of these mutations were necessary.
2019-07-16 | GSE133063 | GEO
Project description:We studies on how a hydrocephalus-causing mutation (R783H) on Trim71 alters Trim71's substrate mRNA binding
2022-11-04 | GSE183715 | GEO