Perivascular spaces in multiple sclerosis point towards neuroinflammation more than neurodegeneration.

2020 ◽  
Author(s):  
Lina Maria Garcia Posada
Keyword(s):  
Multiple Sclerosis ◽  
Perivascular Spaces

Evaluating the Association between Enlarged Perivascular Spaces and Disease Worsening in Multiple Sclerosis

2017 ◽  
Vol 28 (3) ◽  
pp. 273-277 ◽  
Author(s):  
Michele Cavallari ◽  
Svetlana Egorova ◽  
Brian C. Healy ◽  
Miklos Palotai ◽  
Juan Carlos Prieto ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Perivascular Spaces

scholarly journals Enlarged perivascular spaces are not associated with vascular co-morbidities, clinical outcomes, and brain volumes in people with secondary progressive multiple sclerosis

2020 ◽  
Vol 6 (4) ◽  
pp. 205521732096450
Author(s):  
Lindsey Wooliscroft ◽  
Erin Boespflug ◽  
Andrea Hildebrand ◽  
Kathleen Shangraw ◽  
Elizabeth Silbermann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcomes ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Perivascular Spaces ◽  
Centrum Semiovale ◽  
Informative Marker ◽  
Brain Volumes ◽  
Secondary Progressive ◽  
Disability Status

Background In secondary progressive multiple sclerosis (SPMS) significance of enlarged perivascular spaces (ePVS) is unknown. Objectives, Methods: Analysis of associations between vascular co-morbidities, clinical outcomes, and volumetrics with categorical ePVS scores in midbrain, basal ganglia (BG), and centrum semiovale (CSO) in SPMS(n-46). Results, Conclusion: In BG, advancing age (Z = 2.68) and lower Expanded Disability Status Scale (Z = −2.04) were associated with increasing ePVS score. In CSO, advancing age (Z = 2.66) and male gender (Z = 2.45) were associated with increasing ePVS score. No associations between ePVS score and vascular co-morbidities or volumetrics existed; ePVS may not be an informative marker for SPMS.

scholarly journals Hypoperfusion of the Cerebral White Matter in Multiple Sclerosis: Possible Mechanisms and Pathophysiological Significance

2008 ◽  
Vol 28 (10) ◽  
pp. 1645-1651 ◽  
Author(s):  
Jacques De Keyser ◽  
Christel Steen ◽  
Jop P Mostert ◽  
Marcus W Koch
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Adrenergic Receptors ◽  
Perfusion Magnetic Resonance Imaging ◽  
Cerebral White Matter ◽  
Perivascular Spaces ◽  
Axonal Loss ◽  
Normal Appearing White Matter ◽  
Demyelinating Lesions ◽  
The Central Nervous System

Multiple sclerosis (MS) is a disease of the central nervous system characterized by patchy areas of demyelination, inflammation, axonal loss and gliosis, and a diffuse axonal degeneration throughout the so-called normal-appearing white matter (NAWM). A number of recent studies using perfusion magnetic resonance imaging in both relapsing and progressive forms of MS have shown a decreased perfusion of the NAWM, which does not appear to be secondary to axonal loss. The reduced perfusion of the NAWM in MS might be caused by a widespread astrocyte dysfunction, possibly related to a deficiency in astrocytic β2-adrenergic receptors and a reduced formation of cAMP, resulting in a reduced uptake of K+ at the nodes of Ranvier and a reduced release of K+ in the perivascular spaces. Pathologic and imaging studies suggest that ischemic changes might be involved in the development of a subtype of focal demyelinating lesions (type III lesions), and there appears to exist a relationship between decreased white matter perfusion and cognitive dysfunction in patients with MS.

Cell-Based Therapeutic Strategies in Multiple Sclerosis

2014 ◽  
Vol 9 (1) ◽  
pp. 37
Author(s):  
Ian Rossman ◽  
Jeffrey A Cohen ◽  
◽  
Keyword(s):  
Multiple Sclerosis ◽  
Neurological Deficits ◽  
Perivascular Spaces ◽  
Cns Injury ◽  
Surface Receptors ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
Disease Stages ◽  
Ongoing Phase

Multiple sclerosis (MS) is an immune-mediated disease in which acute inflammatory demyelination leads to axonal injury and neurodegeneration, and is manifested clinically by relapsing–remitting neurological deficits superimposed on chronic accumulation of disability. MS treatments are largely immunomodulatory with little, if any, effect on neurodegeneration. Mesenchymal stem cells MSCs) are pluripotent cells derived from adult tissues with intrinsic anti-inflammatory and repair-promoting properties. They cross the blood–brain barrier and target perivascular spaces, which are the sites of inflammatory cell infiltration in MS.In vitro, MSCs can be purified and expanded, labelled for post-transplant tracking and be manipulated to express surface receptors or neurotrophic factors for central nervous system (CNS) targeting or neuroprotection, respectively. Animal models of MS, traumatic CNS injury and neurodegenerative diseases demonstrate clinical and pathological benefits following MSC transplantation. Potentially, MSCs can be used to treat MS patients at various disease stages, which is the current focus of ongoing phase I/II clinical trials at multiple centres.

The central vein sign in multiple sclerosis patients with vascular comorbidities

2020 ◽  
pp. 135245852094378 ◽  
Author(s):  
François Guisset ◽  
Valentina Lolli ◽  
Céline Bugli ◽  
Gaetano Perrotta ◽  
Julie Absil ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Regression Model ◽  
Stepwise Regression ◽  
Univariate Analysis ◽  
Lower Percentage ◽  
Central Vein ◽  
Perivascular Spaces ◽  
Median Frequency ◽  
Multiple Sclerosis Patients ◽  
The Impact

Background: The central vein sign (CVS) is an imaging biomarker able to differentiate multiple sclerosis (MS) from other conditions causing similar appearance lesions on magnetic resonance imaging (MRI), including cerebral small vessel disease (CSVD). However, the impact of vascular risk factors (VRFs) for CSVD on the percentage of CVS positive (CVS+) lesions in MS has never been evaluated. Objective: To investigate the association between different VRFs and the percentage of CVS+ lesions in MS. Methods: In 50 MS patients, 3T brain MRIs (including high-resolution 3-dimensional T2*-weighted images) were analyzed for the presence of the CVS and MRI markers of CSVD. A backward stepwise regression model was used to predict the combined predictive effect of VRF (i.e. age, hypertension, diabetes, obesity, ever-smoking, and hypercholesterolemia) and MRI markers of CSVD on the CVS. Results: The median frequency of CVS+ lesions was 71% (range: 35%–100%). In univariate analysis, age ( p < 0.0001), hypertension ( p < 0.001), diabetes ( p < 0.01), obesity ( p < 0.01), smoking ( p < 0.05), and the presence of enlarged-perivascular-spaces on MRI ( p < 0.005) were all associated with a lower percentage of CVS+ lesions. The stepwise regression model showed that age and arterial hypertension were both associated with the percentage of CVS+ lesions in MS (adjusted R2 = 0.46; p < 0.0001 and p = 0.01, respectively). Conclusion: The proportion of CVS+ lesions significantly decreases in older and hypertensive MS patients. Although this study was conducted in patients with an already established MS diagnosis, the diagnostic yield of the previously proposed 35% CVS proportion-based diagnostic threshold appears to be not affected. Overall these results suggest that the presence of VRF for CSVD should be taken into account during the CVS assessment.

scholarly journals Myelin oligodendrocyte glycoprotein antibody-associated disease: an immunopathological study

Brain ◽  
2020 ◽  
Vol 143 (5) ◽  
pp. 1431-1446 ◽  
Author(s):  
Yoshiki Takai ◽  
Tatsuro Misu ◽  
Kimihiko Kaneko ◽  
Norio Chihara ◽  
Koichi Narikawa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Humoral Immunity ◽  
Demyelinating Disease ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Demyelinating Diseases ◽  
Perivascular Spaces ◽  
Clinical Diagnoses ◽  
Demyelinating Lesions ◽  
Oligoclonal Igg ◽  
Aqp4 Antibody

Abstract Conformation-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG) are detectable in patients with optic neuritis, myelitis, opticomyelitis, acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM) and brainstem/cerebral cortical encephalitis, but are rarely detected in patients with prototypic multiple sclerosis. So far, there has been no systematic study on the pathological relationship between demyelinating lesions and cellular/humoral immunity in MOG antibody-associated disease. Furthermore, it is unclear whether the pathomechanisms of MOG antibody-mediated demyelination are similar to the demyelination patterns of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD) with AQP4 antibody, or ADEM. In this study, we immunohistochemically analysed biopsied brain tissues from 11 patients with MOG antibody-associated disease and other inflammatory demyelinating diseases. Patient median onset age was 29 years (range 9–64), and the median interval from attack to biopsy was 1 month (range 0.5–96). The clinical diagnoses were ADEM (n = 2), MDEM (n = 1), multiple brain lesions without encephalopathy (n = 3), leukoencephalopathy (n = 3) and cortical encephalitis (n = 2). All these cases had multiple/extensive lesions on MRI and were oligoclonal IgG band-negative. Most demyelinating lesions in 10 of 11 cases showed a perivenous demyelinating pattern previously reported in ADEM (153/167 lesions) and a fusion pattern (11/167 lesions) mainly in the cortico-medullary junctions and white matter, and only three lesions in two cases showed confluent demyelinated plaques. In addition, 60 of 167 demyelinating lesions (mainly in the early phase) showed MOG-dominant myelin loss, but relatively preserved oligodendrocytes, which were distinct from those of AQP4 antibody-positive NMOSD exhibiting myelin-associated glycoprotein-dominant oligodendrogliopathy. In MOG antibody-associated diseases, MOG-laden macrophages were found in the perivascular spaces and demyelinating lesions, and infiltrated cells were abundant surrounding multiple blood vessels in and around the demyelinating lesions, mainly consisting of macrophages (CD68; 1814 ± 1188 cells/mm2), B cells (CD20; 468 ± 817 cells/mm2), and T cells (CD3; 2286 ± 1951 cells/mm2), with CD4-dominance (CD4+ versus CD8+; 1281 ± 1196 cells/mm2 versus 851 ± 762 cells/mm2, P &lt; 0.01). Humoral immunity, evidenced by perivascular deposits of activated complements and immunoglobulins, was occasionally observed in some MOG antibody-associated demyelinating lesions, and the frequency was much lower than that in AQP4 antibody-positive NMOSD. Subpial lesions with perivenous demyelination were observed in both ADEM and cortical encephalitis. Our study suggests that ADEM-like perivenous inflammatory demyelination with MOG-dominant myelin loss is a characteristic finding of MOG antibody-associated disease regardless of whether the diagnostic criteria of ADEM are met. These pathological features are clearly different from those of multiple sclerosis and AQP4 antibody-positive NMOSD, suggesting an independent autoimmune demyelinating disease entity.

scholarly journals Initial Immunopathogenesis of Multiple Sclerosis: Innate Immune Response

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Norma Y. Hernández-Pedro ◽  
Guillermo Espinosa-Ramirez ◽  
Verónica Pérez de la Cruz ◽  
Benjamín Pineda ◽  
Julio Sotelo
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Plasma Cells ◽  
Molecular Mimicry ◽  
Innate Immune ◽  
Perivascular Spaces ◽  
Tissue Destruction ◽  
Complex Interactions ◽  
The Central Nervous System ◽  
Mononuclear Cell Infiltrates

Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The hallmark to MS is the demyelinated plaque, which consists of a well-demarcated hypocellular area characterized by the loss of myelin, the formation of astrocytic scars, and the mononuclear cell infiltrates concentrated in perivascular spaces composed of T cells, B lymphocytes, plasma cells, and macrophages. Activation of resident cells initiates an inflammatory cascade, leading to tissue destruction, demyelination, and neurological deficit. The immunological phenomena that lead to the activation of autoreactive T cells to myelin sheath components are the result of multiple and complex interactions between environment and genetic background conferring individual susceptibility. Within the CNS, an increase of TLR expression during MS is observed, even in the absence of any apparent microbial involvement. In the present review, we focus on the role of the innate immune system, the first line of defense of the organism, as promoter and mediator of cross reactions that generate molecular mimicry triggering the inflammatory response through an adaptive cytotoxic response in MS.

scholarly journals A Multiple Sclerosis Patient Benefitting from CSF Flow Enhancement Had Imaging Signs of "Glymphatic-Lymphatic System Disease." Case Report

2021 ◽  
Author(s):  
Antonio Scollato ◽  
Francesco Lolli ◽  
Giancarlo Lastrucci ◽  
Anna Repice ◽  
Giuseppe De Santis ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Lymphatic System ◽  
Immune Surveillance ◽  
Csf Shunt ◽  
Perivascular Spaces ◽  
Primary Progressive Multiple Sclerosis ◽  
Imaging Features ◽  
Csf Flow ◽  
Disease Case ◽  
Flow Enhancement

Abstract Background The derangement of CSF circulation impacts the functions of glymphatic-lymphatic system (G-Ls), which regulates solute trafficking and immune surveillance in the CNS. The imaging features of dilated perivascular spaces imply the substantial impairment of the G-Ls and can be easily estimated It has been proposed that multiple sclerosis can be viewed as a disease involving a failure component and therapeutically could be targeted as such.Case presentationWe report the case of a female patient diagnosed with primary progressive multiple sclerosis, also presenting perivascular spaces dilatation, who transiently improved after CSF shunt diversions. ConclusionsThe G-Ls failure leads to dysregulation of waste molecule clearance in the brain and an altered CNS immune response, potentially in many diseases. The clinical improvement observed in our patient may relate to an increased clearance of inflammatory mediators following the G-Ls reestablishment obtained by CSF flow enhancement.

scholarly journals Enlarged perivascular spaces in multiple sclerosis on magnetic resonance imaging: a systematic review and meta-analysis

2020 ◽  
Vol 267 (11) ◽  
pp. 3199-3212 ◽  
Author(s):  
Tobias Granberg ◽  
Thomas Moridi ◽  
Judith S. Brand ◽  
Susanne Neumann ◽  
Martin Hlavica ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Systematic Review ◽  
Magnetic Resonance ◽  
Small Vessel Disease ◽  
Meta Analysis ◽  
Imaging Biomarker ◽  
Perivascular Spaces ◽  
Resonance Imaging ◽  
Prevalence Odds Ratio

Abstract Background Perivascular spaces can become detectable on magnetic resonance imaging (MRI) upon enlargement, referred to as enlarged perivascular spaces (EPVS) or Virchow-Robin spaces. EPVS have been linked to small vessel disease. Some studies have also indicated an association of EPVS to neuroinflammation and/or neurodegeneration. However, there is conflicting evidence with regards to their potential as a clinically relevant imaging biomarker in multiple sclerosis (MS). Methods To perform a systematic review and meta-analysis of EPVS as visualized by MRI in MS. Nine out of 299 original studies addressing EPVS in humans using MRI were eligible for the systematic review and meta-analysis including a total of 457 MS patients and 352 control subjects. Results In MS, EPVS have been associated with cognitive decline, contrast-enhancing MRI lesions, and brain atrophy. Yet, these associations were not consistent between studies. The meta-analysis revealed that MS patients have greater EPVS prevalence (odds ratio = 4.61, 95% CI = [1.84; 11.60], p = 0.001) as well as higher EPVS counts (standardized mean difference [SMD] = 0.46, 95% CI = [0.26; 0.67], p < 0.001) and larger volumes (SMD = 0.88, 95% CI = [0.19; 1.56], p = 0.01) compared to controls. Conclusions Available literature suggests a higher EPVS burden in MS patients compared to controls. The association of EPVS to neuroinflammatory or -degenerative pathology in MS remains inconsistent. Thus, there is currently insufficient evidence supporting EPVS as diagnostic and/or prognostic marker in MS. In order to benefit future comparisons of studies, we propose recommendations on EPVS assessment standardization in MS. PROSPERO No: CRD42019133946.

Ultrastructural Aspects of Golgi Complex Function in Parathyroid Cells of Winter Frogs

1973 ◽  
Vol 31 ◽  
pp. 680-681
Author(s):  
William J. Dougherty
Keyword(s):  
Golgi Complex ◽  
Secretory Granules ◽  
Complex Function ◽  
Secretory Activity ◽  
Secretory Proteins ◽  
Perivascular Spaces ◽  
Pituitary Cells ◽  
Electron Microscopic ◽  
Ca Ions ◽  
Regulation Of Secretion

The regulation of secretion in exocrine and endocrine cells has long been of interest. Electron microscopic and other studies have demonstrated that secretory proteins synthesized on ribosomes are transported by the rough ER to the Golgi complex where they are concentrated into secretory granules. During active secretion, secretory granules fuse with the cell membrane, liberating and discharging their contents into the perivascular spaces. When secretory activity is suppressed in anterior pituitary cells, undischarged secretory granules may be degraded by lysosomes. In the parathyroid gland, evidence indicates that the level of blood Ca ions regulates both the production and release of parathormone. Thus, when serum Ca is low, synthesis and release of parathormone are both stimulated; when serum Ca is elevated, these processes are inhibited.

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