Glymphatic MRI in idiopathic normal pressure hydrocephalus.
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TLDR
Glymphatic clearance is sleep-dependent and is impaired in patients with normal pressure hydrocephalus, and using MRI, Ringstad et al. visualize the glymphatic system for the first time in humans.Abstract:
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.read more
Citations
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The glymphatic pathway in neurological disorders
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Joanna M. Wardlaw,Helene Benveniste,Berislav V. Zlokovic,Humberto Mestre,Hedok Lee,Fergus N. Doubal,Rosalind Brown,Joel Ramirez,Joel Ramirez,Bradley J. MacIntosh,Bradley J. MacIntosh,Allen Tannenbaum,Lucia Ballerini,Ravi L. Rungta,Davide Boido,Melanie D. Sweeney,Axel Montagne,Serge Charpak,Anne Joutel,Kenneth Smith,Sandra E. Black,Sandra E. Black +21 more
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TL;DR: The ties that bind sleep, aging, Glymphatic clearance, and protein aggregation have shed new light on the pathogenesis of a broad range of neurodegenerative diseases, for which glymphatic failure may constitute a therapeutically targetable final common pathway.
References
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Symptomatic occult hydrocephalus with "normal" cerebrospinal-fluid pressure.a treatable syndrome.
TL;DR: Hydrocephalus is said to be noncommunicating or obstructive if the blockade of circulation is in the ventricular system and communicating or nonobstructive if there is a normal patency of the pathways from the Ventricular system to the lumbar subarachnoid space.
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The Glymphatic System: A Beginner’s Guide
TL;DR: The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular tunnels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system.