scholarly journals SIGLEC1 (CD169): a marker of active neuroinflammation in the brain but not in the blood of multiple sclerosis patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lennard Ostendorf ◽  
Philipp Dittert ◽  
Robert Biesen ◽  
Ankelien Duchow ◽  
Victoria Stiglbauer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neurological Diseases ◽  
Severe Disease ◽  
Myeloid Cells ◽  
Brain Lesions ◽  
Demyelinating Diseases ◽  
Interferon Treatment ◽  
The Central Nervous System ◽  
Multiple Sclerosis Patients ◽  
Almost All

AbstractWe aimed to evaluate SIGLEC1 (CD169) as a biomarker in multiple sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the presence of SIGLEC1+ myeloid cells in demyelinating diseases. We performed flow cytometry-based measurements of SIGLEC1 expression on monocytes in 86 MS patients, 41 NMOSD patients and 31 healthy controls. Additionally, we histologically evaluated the presence of SIGLEC1+ myeloid cells in acute and chronic MS brain lesions as well as other neurological diseases. We found elevated SIGLEC1 expression in 16/86 (18.6%) MS patients and 4/41 (9.8%) NMOSD patients. Almost all MS patients with high SIGLEC1 levels received exogenous interferon beta as an immunomodulatory treatment and only a small fraction of MS patients without interferon treatment had increased SIGLEC1 expression. In our cohort, SIGLEC1 expression on monocytes was—apart from those patients receiving interferon treatment—not significantly increased in patients with MS and NMOSD, nor were levels associated with more severe disease. SIGLEC1+ myeloid cells were abundantly present in active MS lesions as well as in a range of acute infectious and malignant diseases of the central nervous system, but not chronic MS lesions. The presence of SIGLEC1+ myeloid cells in brain lesions could be used to investigate the activity in an inflammatory CNS lesion.

scholarly journals SIGLEC1 (CD169): a marker of active neuroinflammation in the brain but not in the blood of MS patients

2020 ◽  
Author(s):  
Lennard Ostendorf ◽  
Philipp Dittert ◽  
Robert Biesen ◽  
Ankelien Duchow ◽  
Victoria Stiglbauer ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Severe Disease ◽  
Myeloid Cells ◽  
Brain Lesions ◽  
Demyelinating Diseases ◽  
Interferon Treatment ◽  
Immunomodulatory Treatment ◽  
The Central Nervous System ◽  
Almost All ◽  
The Brain

AbstractObjectiveWe aimed to evaluate SIGLEC1 (CD169) as a biomarker in Multiple Sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the specificity of SIGLEC1+ myeloid cells for demyelinating diseasesMethodsWe performed flow cytometry-based measurements of SIGLEC1 expression on monocytes in 86 MS patients, 41 NMOSD patients and 31 healthy controls. Additionally, we histologically evaluated the presence of SIGLEC1+ myeloid cells in acute and chronic MS brain lesions as well as other neurological diseases.ResultsWe found elevated SIGLEC1 expression in 16/86 (18.6%) MS patients and 4/41 (9.8%) NMOSD patients. Almost all MS patients with high SIGLEC1 levels received exogenous interferon beta as an immunomodulatory treatment and only a small fraction of MS patients without interferon treatment had increased SIGLEC1 expression. SIGLEC1+ myeloid cells were abundantly present in active MS lesions as well as in a range of acute infectious and malignant diseases of the central nervous system, but not chronic MS lesions.ConclusionIn our cohort, SIGLEC1 expression on monocytes was – apart from those patients receiving interferon treatment – not significantly increased in patients with MS and NMOSD, nor were levels associated with more severe disease. The presence of SIGLEC1+ myeloid cells in brain lesions could be used to investigate the activity in an inflammatory CNS lesion.

scholarly journals Effects of multiple sclerosis in pregnant and post-birth: particularities of the disease activity

2021 ◽  
Author(s):  
Bianca Barbosa Araldi ◽  
Victor Hugo Gomes ◽  
Bruno Ludvig Vieira ◽  
Klesia Adayani Rodrigues ◽  
Andressa Gabrieli da Silva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Neurological Diseases ◽  
Neuroprotective Effect ◽  
Cumulative Effect ◽  
Demyelinating Diseases ◽  
Hormonal Changes ◽  
Neuroprotective Effects ◽  
Maternal Immune System ◽  
The Central Nervous System

Introduction: Demyelinating diseases are a heterogeneous group of neurological diseases related to autoimmunity whose representative is Multiple Sclerosis (MS). It is characterized by an immune-mediated demyelination of the central nervous system, with a typical outbreak and remission clinic. During pregnancy, a reduction in disease activity was noted due to immunomodulatory effects, and an increase in outbreaks in the puerperium. Thus, our goal is to demonstrate the relationship between pregnancy and MS. Methods: This is a systematic bibliographic review based on searching the SCIELO, PUBMED and UPTODATE databases using the words “Multiple Sclerosis”, “Pregnancy”, “Demyelinating diseases” and “Neurological Disorders”. Discussion: Pregnancy is responsible for numerous changes in the maternal body resulting from hormonal changes with an immunological and neuroprotective effect. Until the beginning of the 20th century, it was considered a risk factor or precipitator of outbreaks in these patients. In 1950, Tillmann et al. questioned him and concluded that pregnancy reduces the risk of outbreaks of the disease and that relapses were more associated with postpartum. The question is still raised by several authors, due to their interest in the search for intricate protective factors in the genesis and cure of the disease. It is believed that immunological changes in pregnancy tend to suppress the maternal immune system preventing fetal rejection, and together with gestational hormones, they are able to make neuronal tissue more resistant to inflammatory aggression and greater capacity for cell repair. In the puerperium, there was an increase in outbreaks of the disease, probably associated with a reduction in hormone levels, the effects of which are lost after the elimination of the fetus. Breastfeeding is not associated with the prevention or risk of new MS outbreaks. The frequency of outbreaks before conception is the only independent predictor of new post-term episodes. There is no consensus regarding the therapeutic approach in these pregnant women. Conclusion: Evidence supports the association between pregnancy, reduced activity of MS and increased activity in the 3 months postpartum, due to the probable loss of neuroprotective effects associated with hormones. Recommendations regarding the use of immunomodulator are suspended before conception (“washout”) until term. New evidence did not associate the use of interferon-β with abortion, cesarean section or low birth weight. There was a benefit of long-term parity with a cumulative effect on the patient’s immunohumor modulation.

An MRI study of Chlamydia pneumoniae infection in Italian multiple sclerosis patients

2003 ◽  
Vol 9 (5) ◽  
pp. 467-471 ◽  
Author(s):  
L ME Grimaldi ◽  
A Pincherle ◽  
F Martinelli-Boneschi ◽  
M Filippi ◽  
F Patti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Chlamydia Pneumoniae ◽  
Neurological Diseases ◽  
Disease Onset ◽  
Progressive Multiple Sclerosis ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
Multiple Sclerosis Patients ◽  
Mri Study

We amplified sequences of the Chlamydia pneumoniae (C P) major-outer membrane protein in the cerebrospinal fluid (CSF) from 23 of 107 (21.5%) relapsing-remitting or secondary progressive multiple sclerosis (MS) patients and two of 77 (2.6%) patients with other neurological diseases (OND) (P =0.00022). C P+ patients showed magnetic resonance imaging (MRI) evidence of more active disease (P =0.02) compared to CP-MS patients and tended to have an anticipation of age at disease onset (32.39-12 versus 28.59-10 years; P =ns) causing a longer disease duration (7.59-5 versus 4.49-4 years; P =0.016) at the time of clinical evaluation. These findings, although indirectly, suggest that C P infection of the central nervous system (C NS) might affect disease course in a subgroup of MS patients.

scholarly journals COVID-19 Immunopathology and the Central Nervous System: Implication for Multiple Sclerosis and Other Autoimmune Diseases with Associated Demyelination

2020 ◽  
Vol 10 (6) ◽  
pp. 345 ◽  
Author(s):  
Marina Kleopatra Boziki ◽  
Alexios-Fotios A. Mentis ◽  
Maria Shumilina ◽  
Gleb Makshakov ◽  
Evgeniy Evdoshenko ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Neurological Diseases ◽  
Demyelinating Diseases ◽  
Relevant Implication ◽  
The Central Nervous System ◽  
Disease Modifying Treatment

In the frame of the coronavirus disease 2019 (COVID-19) pandemic, recent reports on SARS-CoV-2 potential neuroinvasion placed neurologists on increased alertness in order to assess early neurological manifestations and their potentially prognostic value for the COVID-19 disease. Moreover, the management of chronic neurological diseases, such as Multiple Sclerosis (MS), underwent guided modifications, such as an Extended Interval Dose (EID) of Disease-Modifying Treatment (DMT) administration, in order to minimize patients’ exposure to the health system, thus reducing the risk of SARS-CoV-2 infection. In this review, we summarize existing evidence of key immune pathways that the SARS-CoV-2 modifies during COVID-19 and the relevant implication for MS and other autoimmune diseases with associated demyelination (such as Systemic lupus erythematosus and Antiphospholipid syndrome), including the context of potential neuroinvasion by SARS-Cov-2 and the alterations that DMT induces to the immune system. Moreover we hereby aim to provide an overview of the possible consequences that COVID-19 may carry for the Central Nervous System (CNS) in People with MS (PwMS) and other demyelinating diseases, which are likely to pose challenges for treating Neurologists with respect to the long-term disease management of these diseases.

Cold-induced reactivity in multiple sclerosis patients

2017 ◽  
pp. 56-62 ◽  
Author(s):  
Л.И. Герасимова-Мейгал ◽  
И.М. Сиренев
Keyword(s):  
Multiple Sclerosis ◽  
Cold Test ◽  
Typical Feature ◽  
Humid Climate ◽  
Ssr Analysis ◽  
Epidemiological Surveys ◽  
The Central Nervous System ◽  
The Individual ◽  
Hands And Feet ◽  
Multiple Sclerosis Patients

Цель исследования - изучение особенностей восприимчивости пациентов с рассеянным склерозом (РС) к холодовому воздействию с помощью функциональных тестов, характеризующих функцию терморегуляции. Как известно, РС - хроническое прогрессирующее аутоиммунное заболевание центральной нервной системы мультифакториальной природы, более часто встречающееся в регионах с холодным и влажным климатом. Нарушения терморегуляции вследствие автономной дисфункции являются характерным признаком РС, вместе с тем участию холодового фактора в развитии заболевания не придается существенного значения. Методика. Обследовано 32 пациента (17 мужчин и 15 женщин, средний возраст 29,6 ± 4,2 года) с установленным диагнозом: РС ремиттирующе-рецидивирующая форма течения (средняя продолжительность заболевания - 4,2 ± 2,7 года) и 18 практически здоровых лиц группы сравнения. Восприятие холода оценивали с помощью визуально-аналоговой шкалы. Продолжительность холод-индуцированной вазоконстрикции после локального холодового теста изучали по данным инфракрасной термометрии. Вегетативную регуляцию вазомоторных реакций оценивали по результатам анализа вызванных кожных вегетативных потенциалов (ВКВП). Результаты. На основе анализа самооценки восприятия холода у пациентов с РС показана низкая переносимость холодового фактора. При проведении локального холодового теста отмечено замедление восстановления температуры кожи кисти, что характерно для усиления холод-индуцированной вазоконстрикции. В группе пациентов с РС выявлено снижение параметров ВКВП ладоней и стоп, свидетельствующее о дефиците нейрогенного контроля терморегуляционных сосудистых реакций. Заключение. У пациентов с РС выявлены нарушения механизмов терморегуляции при действии холода, что обусловливает высокую индивидуальную восприимчивость к холоду у данной категории лиц. Сопоставление результатов анализа механизмов индивидуальной холод-индуцированной реактивности у пациентов с РС с данными эпидемиологических исследований приводит к заключению о потенциальном модулирующем влиянии холодового фактора на течение РС. The purpose of the present study was focused on the evaluation of the sensitivity to cold in multiple sclerosis (MS) patients by means of functional thermoregulatory based tests. MS is known to be a chronic autoimmune progressive disease of the central nervous system of multifactor origin that is very common in regions with cold and humid climate. Disorder of thermoregulation caused by autonomic dysfunction is a typical feature of MS, however the role of the cold in the disease development is still underestimated. Methods. Thirty two MS patients (17 males, 15 females, mean age 29,6 ± 4,2 years) with the remittent form of the disease (mean disease duration 4,2 ± 2,7 years) and 18 age-matched healthy controls volunteered to participate in this study. Susceptibility to cold was analyzed with the use of visual-analogous scale. The duration of cold-induced vasoconstriction after local cold test was estimated using by infrared thermometry. Autonomic regulation of vasomotor reactions was investigated with the help of the skin sympathetic response (SSR) analysis. Results. The analysis of self-reported perception of the cold in MS patients showed their low tolerance to cold. Slow recovery of the skin temperature of the hand in the local cold test observed in MS patients was considered as the aggravated cold-induced vasoconstriction. The decreased SSR in the hands and feet in MS patients was found that indicates the deficit of the neurogenic control of thermoregulatory vasomotor reactions. Conclusion. The results obtained demonstrate the impairment of thermoregulation under cold in MS patients that leads to higher individual susceptibility to cold of this group. Comparing of the data found in this study on the mechanisms of the individual cold-induced reactivity in MS patients with epidemiological surveys enable to conclude that cold environment has potential modulating effect of on the course of MS.

scholarly journals Ultra-high-field 7-T MRI in multiple sclerosis and other demyelinating diseases: from pathology to clinical practice

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Nicolo’ Bruschi ◽  
Giacomo Boffa ◽  
Matilde Inglese
Keyword(s):  
Multiple Sclerosis ◽  
High Field ◽  
Neurological Diseases ◽  
Lesion Detection ◽  
Demyelinating Diseases ◽  
Metabolic Imaging ◽  
Central Vein ◽  
Ultra High Field ◽  
Functional Features

Abstract Magnetic resonance imaging (MRI) is essential for the early diagnosis of multiple sclerosis (MS), for investigating the disease pathophysiology, and for discriminating MS from other neurological diseases. Ultra-high-field strength (7-T) MRI provides a new tool for studying MS and other demyelinating diseases both in research and in clinical settings. We present an overview of 7-T MRI application in MS focusing on increased sensitivity and specificity for lesion detection and characterisation in the brain and spinal cord, central vein sign identification, and leptomeningeal enhancement detection. We also discuss the role of 7-T MRI in improving our understanding of MS pathophysiology with the aid of metabolic imaging. In addition, we present 7-T MRI applications in other demyelinating diseases. 7-T MRI allows better detection of the anatomical, pathological, and functional features of MS, thus improving our understanding of MS pathology in vivo. 7-T MRI also represents a potential tool for earlier and more accurate diagnosis.

Polypharmacy in chronic neurological diseases: Multiple sclerosis, dementia and Parkinson’s disease

2021 ◽  
Vol 27 ◽  
Author(s):  
Niklas Frahm ◽  
Michael Hecker ◽  
Uwe Zettl
Keyword(s):  
Multiple Sclerosis ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurological Diseases ◽  
Severe Disease ◽  
Inappropriate Medication ◽  
Medication Management ◽  
Chronically Ill ◽  
Symptom Profile ◽  
Quantitative Definition

: Polypharmacy is an important aspect of medication management and particularly affects elderly and chronically ill people. Patients with dementia, Parkinson’s disease (PD) or multiple sclerosis (MS) are at high risk for multimedication due to their complex symptomatology. Our aim was to provide an overview of different definitions of polypharmacy and to present the current state of research on polypharmacy in patients with dementia, PD or MS. The most common definition of polypharmacy in the literature is the concomitant use of ≥5 medications (quantitative definition approach). Polypharmacy rates of up to >50% have been reported for patients with dementia, PD or MS, although MS patients are on average significantly younger than those with dementia or PD. The main predictor of polypharmacy is the complex symptom profile of these neurological disorders. Potentially inappropriate medication (PIM), drug-drug interactions, poor treatment adherence, severe disease course, cognitive impairment, hospitalisation, poor quality of life, frailty and mortality have been associated with polypharmacy in patients with dementia, PD or MS. For patients with polypharmacy, either the avoidance of PIM (selective deprescribing) or the substitution of PIM with more suitable drugs (appropriate polypharmacy) is recommended to achieve a more effective therapeutic management.

Multiple sclerosis risk genotypes correlate with an elevated cerebrospinal fluid level of the suggested prognostic marker CXCL13

2012 ◽  
Vol 19 (7) ◽  
pp. 863-870 ◽  
Author(s):  
M Lindén ◽  
M Khademi ◽  
I Lima Bomfim ◽  
F Piehl ◽  
M Jagodic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Diseases ◽  
Severe Disease ◽  
Human Leukocyte ◽  
Disease Course ◽  
Nucleotide Polymorphisms ◽  
Treatment Protocols ◽  
Tnfaip3 Gene ◽  
Cerebrospinal Fluid Level

Background: The mechanisms of multiple sclerosis (MS) pathogenesis are still largely unknown. The heterogeneity of disease manifestations make the prediction of prognosis and choice of appropriate treatment protocols challenging. Recently, increased cerebrospinal fluid (CSF) levels of the B-cell chemokine CXCL13 was proposed as a possible marker for a more severe disease course and conversion from clinically isolated syndrome (CIS) to relapsing–remitting MS (RRMS). Objective: To investigate whether there are genetic susceptibility variants in MS that correlate with the levels of CXCL13 present in the CSF of MS patients. Methods: We genotyped the human leukocyte antigens HLA-DRB1 and HLA-A, plus a panel of single nucleotide polymorphisms (SNPs) that have been associated with susceptibility to MS and then correlated the genotypes with the levels of CXCL13, as measured with ELISA in the CSF of a total of 663 patients with MS, CIS, other neurological diseases (OND) or OND with an inflammatory component (iOND). Results: Presence of the HLA-DRB1*15 and the MS risk genotypes for SNPs in the RGS1, IRF5 and OLIG3/TNFAIP3 gene regions correlated significantly with increased levels of CXCL13. Conclusion: Our results pointed towards a genetic predisposition for increased CXCL13 levels, which in MS patients correlates with the severity of the disease course. These findings encourage further investigation and replication, in an independent patient cohort.

scholarly journals Metabolomic Signature in Sera of Multiple Sclerosis Patients during Pregnancy

2018 ◽  
Vol 19 (11) ◽  
pp. 3589 ◽  
Author(s):  
Claudia Rossi ◽  
Ilaria Cicalini ◽  
Mirco Zucchelli ◽  
Maria di Ioia ◽  
Marco Onofrj ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Signs ◽  
Female Gender ◽  
Epidemiological Studies ◽  
Mass Spectrometry Analysis ◽  
Spectrometry Analysis ◽  
Hormonal Fluctuations ◽  
The Central Nervous System ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MuS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, neurodegeneration, and degradation of the myelin sheath. Epidemiological studies have shown that the female gender is more susceptible than the male gender to MuS development, with a female-to-male ratio of 2:1. Despite this high onset, women have a better prognosis than men, and the frequency of the relapsing phase decreases during pregnancy, while it increases soon after birth. Therefore, it is interesting to investigate hormonal fluctuations during pregnancy and whether they correlate with metabolic signatures. To gain a deeper inside into the biochemical mechanism of such a multifactorial disease, we adopted targeted metabolomics approaches for the determination of many serum metabolites in 12 pregnant women affected by MuS by mass spectrometry analysis. Our data show a characteristic hormonal fluctuation for estrogens and progesterone, as expected. They also highlight other interesting hormonal alterations for cortisol, corticosterone, 11-deoxycortisol, 4-androstene-3,17-dione, testosterone, and 17α-hydroxyprogesterone. Furthermore, a negative correlation with progesterone levels was observed for amino acids and for acylcarnitines, while an imbalance of different sphingolipids pathways was found during pregnancy. In conclusion, these data are in agreement with the characteristic clinical signs of MuS patients during pregnancy and, if confirmed, they may add an important tessera in the complex mosaic of maternal neuroprotection.

scholarly journals Ozone therapy in ethidium bromide-induced demyelination in rats: possible protective effect [abstract]

2019 ◽  
Vol 3 (4) ◽  
Author(s):  
Mohga Samy
Keyword(s):  
Multiple Sclerosis ◽  
Protective Effect ◽  
Ethidium Bromide ◽  
Demyelinating Diseases ◽  
Immune Reactivity ◽  
Methyl Prednisolone ◽  
The Central Nervous System ◽  
Group 5 ◽  
Group 2 ◽  
Oxygen Groups

BACKGROUND: Multiple sclerosis is an autoimmune inflammatory disease of the central nervous system and it is characterized by excessive demyelination PURPOSE: The study aim to investigate the possible protective effect of ozone (O3) in ethidium bromide (EB) induced demyelination in rats either alone or in combination with corticosteroid in order to decreases the dose of steroid therapy. MATERIAL and METHODS: Rats were divided into 7 groups Group (1) normal control rats received saline. Group (2) sham-operated rats received saline. Group (3) sham operated rats received oxygen. Group (4) EB-treated rats received EB. Group (5) EB treated rats received oxygen. Group (6) EB treated rats received methyl prednisolone (MP) Group (7) EB treated rats received half the dose of MP concomitant with ozone. RESULTS: Significant improvement in the brain serotonin, dopamine, noradrenalin. A reduction of MDA,TNF-COX2 immune-reactivity was noticed in MP and oxygen groups . Furthermore, best amelioration was achieved by combining half the dose of methyl-prednisolone with ozone. CONCLUSION: We concluded that ozone has a protective effect on demyelination and can be used due to its protective effect in demyelinating diseases such as multiple sclerosis.

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