Elevated Concentrations of Soluble Fas and FasL in Multiple Sclerosis Patients with Antinuclear Antibodies

Antinuclear antibodies (ANA) are currently considered as an epiphenomenon of apoptotic processes, possibly in control of autoreactivity in patients with multiple sclerosis (MS). Apoptosis of reactive lymphocytes by the Fas/FasL system is described as an effective control mechanism for autoreactivity in MS. We aimed to provide a context to the potential link between ANA and peripheral lymphocyte apoptosis in MS. The presence of ANA was detected in sera by immunofluorescence assay, and concentrations of sFas and sFasL were determined in the sera of 44 and cerebrospinal fluid (CSF) of 11 relapsing-remitting (RR) MS patients using cytometric bead-based array, and their association with the disease characteristics was determined. ANA were detected in the sera of 43.2% of RRMS patients, and their frequency was the highest in patients with disease duration of less than one year (88,89%). In addition, the number of experienced relapses was lower in ANA-positive patients. Concentrations of sFasL were inversely associated with patients’ expanded disability status scale (EDSS) scores. Low concentrations of both soluble factors strongly discriminated patients with moderate to severe disability, from patients with mild or absent disability only in a group of patients with prolonged disease duration (>10 years). Both soluble mediators were significantly higher in ANA-positive patients. FasL concentrations were inversely associated with the number of relapses. There is a potential link between the presence of ANA and peripheral lymphocyte apoptosis mediated by Fas/FasL system in MS, whose precise role and significance needs to be determined by future mechanistic studies.

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FP14-TU-03 The effect of disease duration on grey matter volume and cognitive performance in relapsing-remitting multiple sclerosis patients

Journal of the Neurological Sciences ◽

10.1016/s0022-510x(09)70337-5 ◽

2009 ◽

Vol 285 ◽

pp. S79 ◽

Cited By ~ 1

Author(s):

A.A. Achiron ◽

S. Tal ◽

D. Magalashvili ◽

A. Achiron

Keyword(s):

Multiple Sclerosis ◽

Cognitive Performance ◽

Grey Matter ◽

Disease Duration ◽

Grey Matter Volume ◽

Matter Volume ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

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Fatty acid binding protein-4 is associated with disability in multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458517750768 ◽

2018 ◽

Vol 25 (3) ◽

pp. 344-351 ◽

Cited By ~ 1

Author(s):

Riley Bove ◽

Brain C Healy ◽

Alexander Musallam ◽

Pejvak Soltany ◽

Camilo Diaz-Cruz ◽

...

Keyword(s):

Multiple Sclerosis ◽

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Disease Duration ◽

Binding Protein ◽

Longitudinal Models ◽

Cross Sectional ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Multiple Sclerosis Patients

Background: Increased adiposity is a risk factor for multiple sclerosis (MS) and is associated with increased disability scores. Adipokines may mediate the effects of adiposity on MS disease course. Objective: The objective of this study is to examine the association between the adipokines (leptin and fatty acid binding protein-4, FABP4) and clinical course in individuals with MS. Methods: Subjects (18–65 years) with relapsing-remitting MS or clinically isolated syndrome and <10 year disease duration were selected from a longitudinal clinical study. Cross-sectional and longitudinal models assessed the relationship between two adipokines (leptin and FABP4) and disease severity in women and men, adjusting for age, disease duration and disease type, Vitamin D level, testosterone level, and as well by body mass index (BMI). Results: Mean age of subjects ( N = 163, 56% women) was 39.3 years. Higher FABP4 levels were associated with higher Expanded Disability Status Scale (EDSS) scores in women in both univariate and multivariate analyses (odds ratio: 1.30; p = 0.005). In men, higher FABP4 level was significantly associated with change in EDSS over time (estimate: 0.0062; p = 0.035). We found no association of FABP4 levels with time to next relapse or a measure of processing speed. Conclusion: FABP4 levels may be associated with increased disability in both men and women with MS independent of effects of BMI and other hormones. Future studies should expand these analyses and further explore downstream mechanisms of adiposity-related effects in MS.

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Bedside Tested Ocular Motor Disorders in Multiple Sclerosis Patients

Multiple Sclerosis International ◽

10.1155/2014/732329 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4 ◽

Cited By ~ 5

Author(s):

G. Servillo ◽

D. Renard ◽

G. Taieb ◽

P. Labauge ◽

S. Bastide ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Duration ◽

Clinically Isolated Syndrome ◽

Motor Disorders ◽

Ocular Motor ◽

Mri Findings ◽

Substantial Impact ◽

Ocular Motor Disorders ◽

Definition Of ◽

Multiple Sclerosis Patients

Background/Aims. Ocular motor disorders (OMDs) are a common feature of multiple sclerosis (MS). In clinical practice, if not reported by patients, OMDs are often underdiagnosed and their prevalence is underestimated.Methods. We studied 163 patients (125 women, 76.7%, 38 men, 23.3%; median age 45.0 years; median disease duration 10 years; median EDSS 3.5) with definite MS (n=150, 92%) or clinically isolated syndrome (n=13, 8%) who underwent a thorough clinical examination of eye movements. Data on localization of previous relapses, MS subtype, and MRI findings were collected and analyzed.Results. Overall, 111/163 (68.1%) patients showed at least one abnormality of eye movement. Most frequent OMDs were impaired smooth pursuit (42.3%), saccadic dysmetria (41.7%), unilateral internuclear ophthalmoplegia (14.7%), slowing of saccades (14.7%), skew deviation (13.5%), and gaze evoked nystagmus (13.5%). Patients with OMDs had more severe disability(P=0.0005)and showed more frequently infratentorial MRI lesions(P=0.004). Localization of previous relapses was not associated with presence of OMDs.Conclusion. OMDs are frequent in patients with stable (no relapses) MS. A precise bedside examination of eye motility can disclose abnormalities that imply the presence of subclinical MS lesions and may have a substantial impact on definition of the diagnosis and on management of MS patients.

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Three-year clinical outcomes of relapsing multiple sclerosis patients treated with dimethyl fumarate in a United States community health center

Multiple Sclerosis Journal ◽

10.1177/1352458517709956 ◽

2017 ◽

Vol 24 (7) ◽

pp. 942-950 ◽

Cited By ~ 12

Author(s):

Kyle Smoot ◽

Kateri J Spinelli ◽

Tamela Stuchiner ◽

Lindsay Lucas ◽

Chiayi Chen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Duration ◽

Community Health Center ◽

Dimethyl Fumarate ◽

Clinical Relapse ◽

Disease Modifying Therapy ◽

Magnetic Resonance Imaging Mri ◽

Multiple Sclerosis Patients ◽

Previous Disease ◽

Relapsing Multiple Sclerosis

Background: Following approval of dimethyl fumarate (DMF), we established a registry of relapsing multiple sclerosis (RMS) patients taking DMF at our community MS center. Objective: To track DMF patients’ tolerability, disease progression, and lymphopenia. Methods: Patients prescribed DMF for RMS from March 2013 to March 2016 were prospectively enrolled ( N = 412). Baseline data, clinical relapses, magnetic resonance imaging (MRI) activity, discontinuation, and lymphocyte counts were captured through chart review. Results: The mean age of patients starting DMF was 49.4 ± 12.0 years and 70% transitioned from a previous disease-modifying therapy (DMT). Of the patients, 38% discontinued DMF, 76% of whom discontinued due to side effects. Clinical relapse and MRI activity were low. Comparing patients who transitioned from interferon-β (IFN), glatiramer acetate (GA), or natalizumab (NTZ), patients previously on NTZ had higher rates of relapse than those previously on GA (annualized relapse rate p = 0.039, percent relapse p = 0.021). Grade III lymphopenia developed in 11% of patients. Lymphopenia was associated with older age ( p < 0.001) and longer disease duration ( p < 0.001). Conclusion: Given the high rates of lymphopenia and discontinuation, it has become our clinical practice to more closely scrutinize older patients and those with a longer disease duration who are potential candidates for initiating DMF therapy.

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Regional Grey Matter Microstructural Changes and Volume Loss Regarding Disease Duration in Multiple Sclerosis Patients

10.21203/rs.3.rs-403709/v1 ◽

2021 ◽

Author(s):

Elisabeth Solana ◽

Eloy Martinez-Heras ◽

Victor Montal ◽

Eduard Vilaplana ◽

Elisabet Lopez-Soley ◽

...

Keyword(s):

Multiple Sclerosis ◽

Grey Matter ◽

Disease Duration ◽

Temporal Cortex ◽

Mean Diffusivity ◽

Volume Loss ◽

Clinical Correlations ◽

Spatio Temporal ◽

Multiple Sclerosis Patients ◽

Microstructural Integrity

Abstract The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a surface-based diffusion MRI processing tool to investigate regional modifications of microstructure and volume loss in GM at different time-points of the disease, and their relationship to disability. We studied 54 healthy controls and 247 MS patients classified according to disease duration: MS1 (less than 5 years, n=67); MS2 (5-15 years, n=107); and MS3 (more than15 years, n=73). We compared GM mean diffusivity (MD) and volume between groups, and estimated their clinical correlations. Regional modifications in MD and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in right putamen. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes extended to more than 80% of regions in MS3 group. Clinical disability was correlated with GM changes. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage.

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Prevalence of chronic cerebrospinal venous insufficiency in multiple sclerosis: a blinded sonographic evaluation

Phlebology The Journal of Venous Disease ◽

10.1177/0268355513512823 ◽

2013 ◽

Vol 30 (1) ◽

pp. 52-60 ◽

Cited By ~ 6

Author(s):

L Tromba ◽

S Blasi ◽

A Vestri ◽

D Kiltzanidi ◽

F Tartaglia ◽

...

Keyword(s):

Multiple Sclerosis ◽

Multivariate Analysis ◽

Scale Score ◽

Healthy Subjects ◽

Venous Insufficiency ◽

Disease Duration ◽

Expanded Disability Status Scale ◽

Chronic Cerebrospinal Venous Insufficiency ◽

Disability Status ◽

Multiple Sclerosis Patients

Objectives: To verify the prevalence of chronic cerebrospinal venous insufficiency in patients affected by different clinical forms of multiple sclerosis and in healthy subjects using the Zamboni ultrasound protocol combined with M-mode ultrasound examination. Materials and methods: We enrolled 112 patients with multiple sclerosis and 67 healthy subjects from 20 to 67 years of age. All the patients underwent Duplex and color-Doppler sonography of the neck vessels, transcranial colour duplex sonography, M-mode study of the valve system and of venous abnormalities. Subjects were positive for chronic cerebrospinal venous insufficiency when at least two of five hemodynamic criteria of the Zamboni protocol were fulfilled. Chronic cerebrospinal venous insufficiency condition was further analyzed by a multivariate analysis including age, sex, disease duration, subtypes of multiple sclerosis and expanded disability status scale score as independent variables. Results: No healthy subjects was positive for chronic cerebrospinal venous insufficiency, while in the sample of patients affected by multiple sclerosis the diagnosis was made in 59.8% of cases ( p < 0.0001). The first criterion was the most frequent in patients affected by multiple sclerosis and chronic cerebrospinal venous insufficiency (respectively 54.4% and 76.1%, p < 0.001). The second, third and fourth criteria were never present in healthy subjects but were detected in patients with multiple sclerosis. The positivity of the second criterion was associated with diagnosis of chronic cerebrospinal venous insufficiency in 100% of cases. The third criterion had a prevalence of 52.2% in the subgroup of chronic cerebrospinal venous insufficiency patients. It was positive in 36 multiple sclerosis patients and was associated with chronic cerebrospinal venous insufficiency diagnosis in all cases except one. The multivariate analysis showed that age, disease duration, sex, subtypes of multiple sclerosis and expanded disability status scale score were not considered predictors of this haemodynamic condition. Conclusion: Chronic cerebrospinal venous insufficiency is a haemodynamic condition strongly associated with multiple sclerosis and is not found in normal controls. The addition of M-mode ultrasound to the diagnostic protocol allows improved observation of venous valve abnormalities.

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Gadopentetate but not gadobutrol accumulates in the dentate nucleus of multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458516670738 ◽

2016 ◽

Vol 23 (7) ◽

pp. 963-972 ◽

Cited By ~ 48

Author(s):

Ludwig Schlemm ◽

Claudia Chien ◽

Judith Bellmann-Strobl ◽

Jan Dörr ◽

Jens Wuerfel ◽

...

Keyword(s):

Multiple Sclerosis ◽

Magnetic Resonance ◽

Dentate Nucleus ◽

Alternative Explanation ◽

Disease Duration ◽

Gadopentetate Dimeglumine ◽

Progressive Neurodegeneration ◽

Magnetic Resonance Imaging Mri ◽

T1 Hyperintensity ◽

Multiple Sclerosis Patients

Background: Previous studies have postulated an association between dentate nucleus T1 hyperintensity and multiple sclerosis (MS)-related progressive neurodegeneration. Therefore, MS patients have been excluded from most studies investigating brain deposition of gadolinium-based contrast agents (GBCAs). Objective: To study the hypothesis that dentate nucleus T1 hyperintensity in MS patients is associated with GBCA administration. Methods: In a cohort of 97 MS patients, the dentate-to-pons signal intensity ratio (DPSIR) was calculated for 265 consecutive T1-weighted magnetic resonance (MR) scans (including sessions with and without the administration of GBCA). Patients exclusively received either gadopentetate dimeglumine (Gd-DTPA, linear) or gadobutrol (Gd-BT-DO3A, macrocyclic). Results: In patients receiving Gd-DTPA, DPSIR increased significantly between the first and the last scan (+0.009, p < 0.001), and following magnetic resonance imaging (MRI) with Gd-DTPA administration as compared to following an MRI without Gd-DTPA administration (+0.005 vs −0.001; p = 0.022). Additionally, there was a positive linear relationship between the number of Gd-DTPA administrations and the increase in DPSIR ( p = 0.017). No DPSIR increase was observed after Gd-BT-DO3A administration. Conclusion: Dentate nucleus T1 hyperintensity in MS patients is associated with Gd-DTPA (but not Gd-BT-DO3A) administration, suggesting an alternative explanation for the association of T1 hyperintensity with disease duration and severity.

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Clinical predictors to cognitive impairment in multiple sclerosis patients

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00292-6 ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Haidy Elshebawy ◽

Ebtesam Mohamed Fahmy ◽

Nervana Mohamed Elfayoumy ◽

Ahmed Mohamed Abdelalim ◽

Rania Shehata Ismail

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Cognitive Dysfunction ◽

Educational Level ◽

Disease Duration ◽

Immunosuppressive Treatment ◽

Clinical Predictors ◽

Physical Handicap ◽

Frequent Relapses ◽

Multiple Sclerosis Patients

Abstract Background Cognitive dysfunction is increasingly recognized in multiple sclerosis, even in the early phase of the disease. Multiple sclerosis patients with even mild cognitive deficits may experience greater difficulties in social contact and daily activities, irrespective of physical handicap. This study aimed to estimate clinical predictors of cognitive dysfunction in a sample of Egyptian people with MS. Results Significant worse performance in assessed cognitive scales was observed in people with MS as compared to controls. This was related to low educational level, long disease duration, initial cerebellar and motor attacks, progressive course, frequent relapses, and immunosuppressive medications. Cognitive assessment scales were significantly negatively correlated with disability measured by Expanded Disability Status Scale (EDSS) scores. Conclusion Predictors of cognitive impairment in people with MS were low educational level, longer disease duration, type of initial attack, frequent relapses, progressive form, higher clinical disability, and immunosuppressive treatment.

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