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Clinical Correlation of Abnormal Findings on Magnetic Resonance Elastography in Idiopathic Normal Pressure Hydrocephalus.

ABSTRACT: Idiopathic normal pressure hydrocephalus (iNPH) is a ventriculomegaly syndrome characterized by dementia, urinary incontinence, and gait disturbance, which is potentially reversible after ventriculoperitoneal shunting (VPS). Magnetic resonance elastography (MRE) is an evolving imaging technology that noninvasively measures tissue viscoelasticity. We studied iNPH patients using MRE prior to shunting, compared them with normal controls, and analyzed associations between MRE findings and clinical features, as a pilot assessment of MRE in iNPH.Stiffness values were measured on preoperative MRE in 10 iNPH patients scheduled for VPS and compared with those in 20 age- and sex-matched controls. Stiffness results were correlated with clinical iNPH symptoms.MRE demonstrated significantly increased stiffness in iNPH in cerebrum (P = 0.04), occipital (P = 0.002), and parietal (P = 0.01) regions of interest (ROIs) and significantly decreased stiffness in periventricular ROIs (P < 0.0001). Stiffness was not significantly different in frontal (P = 0.1) and deep gray ROIs (P = 0.4). Univariate analysis showed associations between preoperative iNPH symptoms and abnormally increased stiffness, including urinary incontinence with cerebrum (P = 0.005), frontal (P = 0.04), and cerebellum (P = 0.03) ROIs, and Parkinsonism with occipital ROI (P = 0.04). Postoperative improvement was associated with increased deep gray stiffness (P = 0.01); failure was associated with increased temporal (P = 0.0002) stiffness.Based on the preliminary results of this small, limited analysis, brain stiffness may be altered in iNPH, and these alterations in parenchymal viscoelastic properties may be correlated with clinical symptoms. Increased temporal stiffness may predict surgical failure and potentially suggest an alternative dementing pathology underlying the iNPH-like symptoms. These findings highlight the potential future utility of MRE in iNPH management.

SUBMITTER: Perry A

PROVIDER: S-EPMC5357459 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Clinical Correlation of Abnormal Findings on Magnetic Resonance Elastography in Idiopathic Normal Pressure Hydrocephalus.

Perry Avital A Graffeo Christopher S CS Fattahi Nikoo N ElSheikh Mona M MM Cray Nealey N Arani Arvin A Ehman Richard L RL Glaser Kevin J KJ Manduca Armando A Meyer Fredric B FB Huston John J

World neurosurgery 20170105

<h4>Background</h4>Idiopathic normal pressure hydrocephalus (iNPH) is a ventriculomegaly syndrome characterized by dementia, urinary incontinence, and gait disturbance, which is potentially reversible after ventriculoperitoneal shunting (VPS). Magnetic resonance elastography (MRE) is an evolving imaging technology that noninvasively measures tissue viscoelasticity. We studied iNPH patients using MRE prior to shunting, compared them with normal controls, and analyzed associations between MRE find ...[more]

PMID: 28063896

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Project description:BackgroundThe significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) is unknown.ObjectiveTo investigate the role of soluble APP (sAPP) and amyloid beta (A?) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy A? and hyperphosphorylated tau (HP?) findings.MethodsThe study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against A? and HP?. CSF levels of AD-related biomarkers (A?42, p-tau, total tau), non-AD-related A? isoforms (A?38, A?40), sAPP isoforms (sAPP?, sAPP?), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE.ResultsLumbar CSF levels of sAPP? were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPP? showed a similar trend (p?=?0.06). CSF sAPP isoform levels showed no association to A? or HP? in the brain biopsy. Quantified A? load in the brain biopsy showed a negative correlation with CSF levels of A?42 in ventricular (r?=?-0.295, p?=?0.003) and lumbar (r?=?-0.356, p?=?0.01) samples, while the levels of A?38 and A?40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure.ConclusionsThe role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD.

Project description:Disturbed clearance of toxic metabolites from the brain via cerebrospinal fluid is emerging as an important mechanism behind dementia and neurodegeneration. To this end, magnetic resonance imaging work-up of dementia diseases is largely focused on anatomical derangements of the brain. This study explores magnetic resonance imaging biomarkers of cerebrospinal fluid tracer dynamics in patients with the dementia subtype idiopathic normal pressure hydrocephalus and a cohort of reference subjects. All study participants underwent multi-phase magnetic resonance imaging up to 48 h after intrathecal administration of the contrast agent gadobutrol (0.5 ml, 1 mmol/ml), serving as cerebrospinal fluid tracer. Imaging biomarkers of cerebrospinal fluid tracer dynamics (i.e. ventricular reflux grades 0-4 and clearance) were compared with anatomical magnetic resonance imaging biomarkers of cerebrospinal fluid space anatomy (Evans' index, callosal angle and disproportional enlargement of subarachnoid spaces hydrocephalus) and neurodegeneration (Schelten's medial temporal atrophy scores, Fazeka's scores and entorhinal cortex thickness). The imaging scores were also related to a pulsatile intracranial pressure score indicative of intracranial compliance. In shunt-responsive idiopathic normal pressure hydrocephalus, the imaging biomarkers demonstrated significantly altered cerebrospinal fluid tracer dynamics (ventricular reflux grades 3-4 and reduced clearance of tracer), deranged cerebrospinal fluid space anatomy and pronounced neurodegeneration. The altered MRI biomarkers were accompanied by pressure indices of impaired intracranial compliance. In conclusion, we present novel magnetic resonance imaging biomarkers characterizing idiopathic normal pressure hydrocephalus pathophysiology, namely measures of cerebrospinal fluid molecular redistribution and clearance, which add information to traditional imaging scores of cerebrospinal fluid space anatomy and neurodegeneration.

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.

Dataset Information

Clinical Correlation of Abnormal Findings on Magnetic Resonance Elastography in Idiopathic Normal Pressure Hydrocephalus.

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Clinical Correlation of Abnormal Findings on Magnetic Resonance Elastography in Idiopathic Normal Pressure Hydrocephalus.

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