scholarly journals Changes in Cerebrospinal Fluid Balance of TNF and TNF Receptors in Naïve Multiple Sclerosis Patients: Early Involvement in Compartmentalised Intrathecal Inflammation

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1712
Author(s):  
Roberta Magliozzi ◽  
Francesco Pezzini ◽  
Mairi Pucci ◽  
Stefania Rossi ◽  
Francesco Facchiano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Protein Pattern ◽  
Fold Change ◽  
Cortical Lesion ◽  
Control Group ◽  
Lesion Volume ◽  
Mri Features ◽  
Csf Levels ◽  
Multiple Sclerosis Patients

An imbalance of TNF signalling in the inflammatory milieu generated by meningeal immune cell infiltrates in the subarachnoid space in multiple sclerosis (MS), and its animal model may lead to increased cortical pathology. In order to explore whether this feature may be present from the early stages of MS and may be associated with the clinical outcome, the protein levels of TNF, sTNF-R1 and sTNF-R2 were assayed in CSF collected from 122 treatment-naïve MS patients and 36 subjects with other neurological conditions at diagnosis. Potential correlations with other CSF cytokines/chemokines and with clinical and imaging parameters at diagnosis (T0) and after 2 years of follow-up (T24) were evaluated. Significantly increased levels of TNF (fold change: 7.739; p < 0.001), sTNF-R1 (fold change: 1.693; p < 0.001) and sTNF-R2 (fold change: 2.189; p < 0.001) were detected in CSF of MS patients compared to the control group at T0. Increased TNF levels in CSF were significantly (p < 0.01) associated with increased EDSS change (r = 0.43), relapses (r = 0.48) and the appearance of white matter lesions (r = 0.49). CSF levels of TNFR1 were associated with cortical lesion volume (r = 0.41) at T0, as well as with new cortical lesions (r = 0.56), whilst no correlation could be found between TNFR2 levels in CSF and clinical or MRI features. Combined correlation and pathway analysis (ingenuity) of the CSF protein pattern associated with TNF expression (encompassing elevated levels of BAFF, IFN-γ, IL-1β, IL-10, IL-8, IL-16, CCL21, haptoglobin and fibrinogen) showed a particular relationship to the interaction between innate and adaptive immune response. The CSF sTNF-R1-associated pattern (encompassing high levels of CXCL13, TWEAK, LIGHT, IL-35, osteopontin, pentraxin-3, sCD163 and chitinase-3-L1) was mainly related to altered T cell and B cell signalling. Finally, the CSF TNFR2-associated pattern (encompassing high CSF levels of IFN-β, IFN-λ2, sIL-6Rα) was linked to Th cell differentiation and regulatory cytokine signalling. In conclusion, dysregulation of TNF and TNF-R1/2 pathways associates with specific clinical/MRI profiles and can be identified at a very early stage in MS patients, at the time of diagnosis, contributing to the prediction of the disease outcome.

Assessment of biochemical determinants in Multiple Sclerosis patients following the oral administration of β-D-Mannuronic acid [M2000]

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohamad Reza Nikouei Moghaddam ◽  
Monireh Movahedi ◽  
Maryam Bananej ◽  
Soheil Najafi ◽  
Nahid Beladi Moghadam ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Uric Acid ◽  
Vitamin D3 ◽  
Chronic Inflammatory Disease ◽  
Toxic Effects ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mannuronic Acid ◽  
Anti Inflammatory ◽  
Multiple Sclerosis Patients

Background: Multiple sclerosis is an autoimmune chronic inflammatory disease of the central nervous system that can lead to some serious disabilities. Despite using various immunomodulatory and anti-inflammatory drugs that have therapeutic effects, they cannot reduce its progression completely, and have some unwanted side effects too. The immunomodulatory and anti-inflammatory effects of the β-D-Mannuronic acid [M2000] have been proven in several surveys, and the present research was designed to determine its toxicity and therapeutic effects in MS patients. Methods: This study was performed on 15 MS patients who took 25 mg/kg/day the oral form of the β-D-Mannuronic acid for six months, and 15 healthy people as a control group. Serum levels of Urea, Creatinine, GGT, Vitamin D3, Uric acid, and Anti-Phospholipids were compared to evaluate the therapeutic and possible toxic effects of this drug after this period. Results: Non- toxic effects through the study of Urea, Creatinine, GGT, and non-significant changes in Uric acid and AntiPhospholipids levels, besides a significant rise in Vitamin, D3 levels in the M2000 treated cases were found. Conclusions: Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity when administered orally and also has some therapeutic effects in MS patients.

Cognitive deficit is related to immune-cell beta-NGF in multiple sclerosis patients

2012 ◽  
Vol 321 (1-2) ◽  
pp. 43-48 ◽  
Author(s):  
Alicja Kalinowska-Łyszczarz ◽  
Mikołaj A. Pawlak ◽  
Sławomir Michalak ◽  
Jacek Losy
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Deficit ◽  
Immune Cell ◽  
Multiple Sclerosis Patients

Fatigue, mood and quality of life improve in MS patients after progressive resistance training

2010 ◽  
Vol 16 (4) ◽  
pp. 480-490 ◽  
Author(s):  
U. Dalgas ◽  
E. Stenager ◽  
J. Jakobsen ◽  
T. Petersen ◽  
HJ Hansen ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Resistance Training ◽  
Beneficial Effect ◽  
Control Group ◽  
Progressive Resistance Training ◽  
Multiple Sclerosis Patients ◽  
Progressive Resistance

Fatigue occurs in the majority of multiple sclerosis patients and therapeutic possibilities are few. Fatigue, mood and quality of life were studied in patients with multiple sclerosis following progressive resistance training leading to improvement of muscular strength and functional capacity. Fatigue (Fatigue Severity Scale, FSS), mood (Major Depression Inventory, MDI) and quality of life (physical and mental component scores, PCS and MCS, of SF36) were scored at start, end and follow-up of a randomized controlled clinical trial of 12 weeks of progressive resistance training in moderately disabled (Expanded Disability Status Scale, EDSS: 3—5.5) multiple sclerosis patients including a Control group ( n = 15) and an Exercise group ( n = 16). Fatigue (FSS > 4) was present in all patients. Scores of FSS, MDI, PCS—SF36 and MCS—SF36 were comparable at start of study in the two groups. Fatigue improved during exercise by —0.6 (95% confidence interval (CI) —1.4 to 0.4) a.u. vs. 0.1 (95% CI —0.4 to 0.6) a.u. in controls ( p = 0.04), mood improved by —2.4 (95% CI —4.1 to 0.7) a.u. vs. 1.1 (—1.2 to 3.4) a.u. in controls ( p = 0.01) and quality of life (PCS—SF36) improved by 3.5 (95% CI 1.4—5.7) a.u. vs. —1.0 (95% CI —3.4—1.4) a.u. in controls ( p = 0.01). The beneficial effect of progressive resistance training on all scores was maintained at follow-up after further 12 weeks. Fatigue, mood and quality of life all improved following progressive resistance training, the beneficial effect being maintained for at least 12 weeks after end of intervention.

scholarly journals Effect of a Combined Program of Strength and Dual Cognitive-Motor Tasks in Multiple Sclerosis Subjects

2020 ◽  
Vol 17 (17) ◽  
pp. 6397
Author(s):  
Carmen Gutiérrez-Cruz ◽  
F.Javier Rojas-Ruiz ◽  
Juan Carlos De la Cruz-Márquez ◽  
Marcos Gutiérrez-Dávila
Keyword(s):  
Multiple Sclerosis ◽  
Training Program ◽  
Force Measurement ◽  
Intervention Group ◽  
Daily Activities ◽  
Control Group ◽  
Motor Tasks ◽  
Dual Tasking ◽  
Combined Training ◽  
Multiple Sclerosis Patients

This study investigated the effects of a 24-week combined training program (CTP) based on strength exercises and cognitive–motor tasks performed concurrently in participants with multiple sclerosis. A randomized, controlled intervention study was carried out. In total, 31 subjects with a confirmed diagnosis of multiple sclerosis (14 men and 17 women) were stratified and randomized into an intervention group (17 subjects) and a control group (14 subjects). The intervention group completed three weekly training sessions for 24 weeks, while the control group pursued their normal daily activities. In this program, cognitive–motor tasks were completed at once (dual tasking). A 3D photogrammetry connected to a selective attention system designed for dual tasking while walking was used. Ground reaction forces were measured using two force plates, one for sit-to-stand testing, while the other was used for static force measurement. Postural equilibrium was examined using a stabilometric plate based for Romberg test assessment. The 24-week training program for multiple sclerosis patients improved their static peak force by 11% (p < 0 .05), their rate of force development by 36% (p < 0.05), and their balance (p < 0.05). Performance in daily activities such as walking or sitting-to-standing improved significantly in multiple sclerosis participants. CTP training was effective in reducing the dual-task costs of step length (48%) and walking velocity (54%), as compared to a matched control group.

The efficacy of multidisciplinary rehabilitation in stable multiple sclerosis patients

2006 ◽  
Vol 12 (2) ◽  
pp. 235-242 ◽  
Author(s):  
L K Storr ◽  
P S Sørensen ◽  
M Ravnborg
Keyword(s):  
Multiple Sclerosis ◽  
Outcome Measures ◽  
Bodily Pain ◽  
Intervention Group ◽  
Inpatient Rehabilitation ◽  
Control Group ◽  
Double Blind ◽  
Multidisciplinary Rehabilitation ◽  
Upper Limb Function ◽  
Multiple Sclerosis Patients

Objective To evaluate the short-term efficacy of multidisciplinary, inpatient rehabilitation of multiple sclerosis (MS) patients. Methods A double-blind, randomized, parallel group design was used. The intervention group were offered comprehensive, multidisciplinary inpatient rehabilitation at the Haslev MS Hospital for an average of 35.5 days, while the control group received no treatment related to the study. All patients were examined in their homes twice with a 10-week interval. The rehabilitation of the intervention group started 2-3 weeks after the first examination and ended 2-3 weeks before the second examination. Impairment was assessed by the Multiple Sclerosis Impairment Scale and the Expanded Disability Status Scale. Disability was assessed by means of Guy’s Neurological Disability Scale. Two specific scales were used to assess upper limb function and ambulation: The Nine-Hole Peg Test and timed 10-metre walking. Patients’ own perception of bodily pain, bladder symptoms, spasticity, fatigue, impaired walking and transfers were recorded using visual analogue scales. Finally, quality of life was assessed using the Life Appreciation and Satisfaction Questionnaire and the Functional Assessment in Multiple Sclerosis. Patients Two hundred and thirty-three patients were screened and of those 38 were included for treatment and 52 as controls. Results We found no statistically significant differences between the two groups in any of the outcome measures. Conclusion Although the study was underpowered, the negative outcome exposes the difficulties in quantitative analyses of the efficacy of multidisciplinary rehabilitation, which is liable to confounding factors such as variation in the indication for treatment, in the placebo effect, and in the reliability and responsiveness of the outcome measures.

scholarly journals Inflammatory Demyelinating Central Nervous System Diseases in Childhood: Clinical and Paraclinical Profiles in 133 Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
Derya Kaya ◽  
Egemen İdiman ◽  
Serkan Özakbaş
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Disease Onset ◽  
Progressive Multiple Sclerosis ◽  
Western Turkey ◽  
Mri Features ◽  
Cranial Mri ◽  
Multiple Sclerosis Patients ◽  
Demyelinating Disorders

In a retrospective review of patients with acquired demyelinating disorders of the central nervous system, 133 patients (5.6%) whose diseases started in childhood, were selected from 2369 patients, who had medical records in the Neurology Department of Dokuz Eylul University. Out of 133, 98 had relapsing remitting multiple sclerosis, 21 had secondary progressive multiple sclerosis, 8 had clinically isolated syndrome, 3 had neuromyelitis optica, 2 had Marburg disease, and 1 had radiologically isolated syndrome. In 55 patients (41.3%), disease onset was before age 16. Polysymptomatic presentation (22.6%) was the most common initial feature. The EDSS scores ranged from 0 to 9 with a median of 2.0 () for 126 patients. MRI records of 111 patients were obtained. 97 patients had clinically definite multiple sclerosis. 11 MS patients (11.3%) did not initially present the diagnostic MRI features. All of the remaining multiple sclerosis patients fulfilled Barkhof-Tintore criteria (100%) and 88.7% fulfilled KIDMUS criteria. Cranial MRI of NMO patients was normal. Our findings demonstrate some important clinical and paraclinical features that can help the literature on acquired demyelinating disorders of childhood by utilizing data from Western Turkey.

Neuropsychological impairment in multiple sclerosis patients: the role of (juxta)cortical lesion on FLAIR

2000 ◽  
Vol 6 (4) ◽  
pp. 280-285 ◽  
Author(s):  
R.H.C. Lazeron ◽  
D.W. Langdon ◽  
M. Filippi ◽  
J.H.T.M. van Waesberghe ◽  
V.L. Stevenson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuropsychological Impairment ◽  
Cortical Lesion ◽  
Multiple Sclerosis Patients

T1 cortical hypointensities and their association with cognitive disability in multiple sclerosis

2010 ◽  
Vol 16 (10) ◽  
pp. 1203-1212 ◽  
Author(s):  
Francesca Bagnato ◽  
Zeena Salman ◽  
Robert Kane ◽  
Sungyoung Auh ◽  
Fredric K Cantor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
White Matter ◽  
Statistical Significance ◽  
Verbal Learning ◽  
Lesion Volume ◽  
Cognitive Disability ◽  
3.0 Tesla ◽  
Multiple Sclerosis Patients ◽  
The Impact

Background: Neocortical lesions (NLs) largely contribute to the pathology of multiple sclerosis (MS), although their relevance in patients’ disability remains unknown. Objective: To assess the incidence of T1 hypointense NLs by 3.0-Tesla magnetic resonance imaging (MRI) in patients with MS and examine neocortical lesion association with cognitive impairment. Methods: In this case-control study, 21 MS patients and 21 age-, sex- and years of education-matched healthy volunteers underwent: (i) a neuropsychological examination rating cognitive impairment (Minimal Assessment of Cognitive Function in MS); (ii) a 3.0-Tesla MRI inclusive of an isotropic 1.0 mm3 three-dimensional inversion prepared spoiled gradient-recalled-echo (3D-IRSPGR) image and T1- and T2-weighted images. Hypointensities on 3D-IRSPGR lying in the cortex, either entirely or partially were counted and association between NLs and cognitive impairment investigated. Results: A total of 95 NLs were observed in 14 (66.7%) patients. NL+ patients performed poorer (p = 0.020) than NLpatients only on the delayed recall component of the California Verbal Learning Test. This difference lost statistical significance when a correction for white matter lesion volume was employed. Conclusions: Although T 1 hypointense NLs may be present in a relatively high proportion of multiple sclerosis patients, the impact that they have in cognitive impairment is not independent from white matter disease.

scholarly journals Axonal Damage in Multiple Sclerosis Patients with High versus Low Expanded Disability Status Scale Score

2004 ◽  
Vol 31 (2) ◽  
pp. 225-228 ◽  
Author(s):  
Steven D. Brass ◽  
Sridar Narayanan ◽  
Jack P. Antel ◽  
Yves Lapierre ◽  
Louis Collins ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Magnetic Resonance ◽  
Disease Process ◽  
Resonance Spectroscopy ◽  
Lesion Volume ◽  
Spinal Cord Atrophy ◽  
Neuronal Marker ◽  
Multiple Sclerosis Patients

AbstractBackground:The pathophysiological basis for differences in disability in patients with multiple sclerosis is unclear.Methods:We used magnetic resonance imaging to examine whether differences in disability in cohorts of multiple sclerosis patients with similar T2-weighted lesion volume and disease duration were associated with a more destructive disease process in the more disabled patients.Results:The benign and severely disabled groups had similar brain atrophy metrics and similar decreases of the neuronal marker, N-acetylaspartate, in the normal appearing white matter of the cerebrum on magnetic resonance spectroscopy examination in vivo. The severely disabled cohort had more spinal cord atrophy.Conclusion:The dissociation of spinal cord atrophy and cerebral atrophy between these two groups suggests that the difference between the more benign and more disabled groups cannot be explained by a more aggressive pathological process that is affecting the entire neuroaxis in a homogeneous fashion.

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