MR Elastography-Based Assessment of Matrix Remodeling at Lesion Sites Associated With Clinical Severity in a Model of Multiple Sclerosis

Magnetic resonance imaging (MRI) with gadolinium based contrast agents (GBCA) is routinely used in the clinic to visualize lesions in multiple sclerosis (MS). Although GBCA reveal endothelial permeability, they fail to expose other aspects of lesion formation such as the magnitude of inflammation or tissue changes occurring at sites of blood-brain barrier (BBB) disruption. Moreover, evidence pointing to potential side effects of GBCA has been increasing. Thus, there is an urgent need to develop GBCA-independent imaging tools to monitor pathology in MS. Using MR-elastography (MRE), we previously demonstrated in both MS and the animal model experimental autoimmune encephalomyelitis (EAE) that inflammation was associated with a reduction of brain stiffness. Now, using the relapsing-remitting EAE model, we show that the cerebellum—a region with predominant inflammation in this model—is especially prone to loss of stiffness. We also demonstrate that, contrary to GBCA-MRI, reduction of brain stiffness correlates with clinical disability and is associated with enhanced expression of the extracellular matrix protein fibronectin (FN). Further, we show that FN is largely expressed by activated astrocytes at acute lesions, and reflects the magnitude of tissue remodeling at sites of BBB breakdown. Therefore, MRE could emerge as a safe tool suitable to monitor disease activity in MS.
Source: Frontiers in Neurology - Category: Neurology Source Type: research

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Publication date: Available online 4 February 2020Source: Multiple Sclerosis and Related DisordersAuthor(s): Eun Bin Cho, Hye-Jin Cho, Misong Choi, Jin Myoung Seok, Hee Young Shin, Byoung Joon Kim, Ju-Hong MinAbstractBackground: Altered lipid metabolism is a feature of systemic autoimmune diseases. Dyslipidemia is associated with the disease activity and progression in patients with multiple sclerosis (MS). However, in neuromyelitis optica spectrum disorder (NMOSD), changes in the lipid profile and the associations between specific lipid levels and disease activity/disability are unknown.Methods: Serum samples (N = 148...
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
We report the case of a 41-year-old patient suffering from primary progressive (PP) MS who presented after 16  months of treatment with high doses of biotin (QIZENDAY) with worsening of his Expanding Disability Status Scale (EDSS) score and the appearance of a symptomatic new T2 pseudo-tumoural lesion on brain magnetic resonance imaging (MRI), suggestive of tardive inflammatory reactivation possibly due to the biotin. The newer and more effective therapies for MS are, however, associated with risks that necessitate an active management strategy and continuous vigilance. Physicians should be aware of iatrogenic neurolo...
Source: Neurology and Therapy - Category: Neurology Source Type: research
ConclusionMS in Kuwait seems to have an earlier age at onset. There is significant gender difference in mental health impairment among patients. Future interventions should be directed toward women, low-income, and non-Kuwaiti-Arabs. The estimated prevalence is based on self-reported data, tertiles as cut-off points, and hence should be interpreted with caution. PDQ and MHI are MSQOLI scales used as screening tools that don't correlate well with an objective test and shouldn't replace objective measures of physical and cognitive function tests including expanded disability status scale or magnetic resonance imaging.
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
ABSTRACT Multiple sclerosis (MS) is an autoimmune, inflammatory, and degenerative disease of the central nervous system. Axonal degeneration is triggered by inflammation and is the pathological substrate of progressive disability in patients with MS. Therapeutic interventions can reduce inflammatory activity, thus delaying neurodegeneration and the progression of disability. Disease activity and neurodegeneration are assessed mainly through clinical evaluation and magnetic resonance imaging. These measures lack sensitivity and accuracy, so new biomarkers are necessary. Several markers have been studied and to date the most...
Source: Arquivos de Neuro-Psiquiatria - Category: Neurology Source Type: research
Iris Lavon1,2†, Coral Heli1†, Livnat Brill1, Hanna Charbit1,2 and Adi Vaknin-Dembinsky1* 1Department of Neurology and Laboratory of Neuroimmunology, and the Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel 2Leslie and Michael Gaffin Center for Neuro-Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel Background: The clinical course of multiple sclerosis ranges from benign with little disease progression and minimal disability, to severe disease requiring intensive medical treatment. There are no reliable circulating biomarkers fo...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: Seizures and encephalopathy are not rare in MOG encephalomyelitis, and are commonly associated with cortical and subcortical brain lesions. MOG-encephalomyelitis often presents with clinical meningoencephalitis symptoms and abnormal CSF findings mimicking central nervous system infection in pediatric and young adult patients. Background Immunoglobulin-G against myelin oligodendrocyte glycoprotein (MOG-IgG) is considered a potential demyelinating disease-associated autoantibody. Previous experimental studies have established MOG-IgG as a pathogenic antigen rather than an epiphenomenal bystander or a secon...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Conclusions OCB are important biomarkers that can support MRI diagnostics and help to avoid false-positive MS diagnoses. Therefore, the revised McDonalds criteria have increased the importance of the OCB. New biomarkers such as AQP4 have now established themselves in clinical practice, and others such as Anti-MOG and NfL are about to enter clinical routine. An important focus in the search for new biomarkers is the monitoring of therapy efficacy and the prediction of severe side effects. Many other CSF molecules such as CHI3L1, IL-6, or CXCL13 show potential as markers for clinical practice, but further research is nee...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions The momentous advances in spinal imaging in ALS suggest the spinal metrics may soon be used as validated diagnostic, monitoring, and prognostic markers, contributing both to individualized patient care and pharmacological trials. Author Contributions ME, GQ, PB, and P-FP contributed equally to the conceptualization, drafting, and revision of the manuscript. Funding Peter Bede is supported by the Health Research Board (HRB—Ireland; HRB EIA-2017-019), the Iris O'Brien Foundation, the Irish Institute of Clinical Neuroscience IICN—Novartis Ireland Research Grant, and the Research Motor Neur...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Graham Cooper1,2,3, Carsten Finke2,4, Claudia Chien1,3, Alexander U. Brandt1,3,5, Susanna Asseyer1,3, Klemens Ruprecht6, Judith Bellmann-Strobl1,3, Friedemann Paul1,2,3,6*† and Michael Scheel1,3,7† 1NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany 2Einstein Center for Neurosciences, Berlin, Germany 3Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité – Universitä...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
In this study, we show that calorie restriction is protective against age-related increases in senescence and microglia activation and pro-inflammatory cytokine expression in an animal model of aging. Further, these protective effects mitigated age-related decline in neuroblast and neuronal production, and enhanced olfactory memory performance, a behavioral index of neurogenesis in the SVZ. Our results support the concept that calorie restriction might be an effective anti-aging intervention in the context of healthy brain aging. Greater Modest Activity in Late Life Correlates with Lower Incidence of Dementia ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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