Spatiotemporal distribution of white matter lesions in relapsing–remitting and secondary progressive multiple sclerosis

2012 ◽  
Vol 18 (11) ◽  
pp. 1577-1584 ◽  
Author(s):  
Lukas Filli ◽  
Louis Hofstetter ◽  
Pascal Kuster ◽  
Stefan Traud ◽  
Nicole Mueller-Lenke ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Disease Progression ◽  
Spatiotemporal Distribution ◽  
Centrum Semiovale ◽  
Cross Sectional ◽  
Secondary Progressive ◽  
Lateral Ventricles ◽  
Relapsing Remitting ◽  
T1 And T2

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. MS lesions show a typical distribution pattern and primarily affect the white matter (WM) in the periventricular zone and in the centrum semiovale. Objective: To track lesion development during disease progression, we compared the spatiotemporal distribution patterns of lesions in relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS). Methods: We used T1 and T2 weighted MR images of 209 RRMS and 62 SPMS patients acquired on two different 1.5 Tesla MR scanners in two clinical centers followed up for 25 (± 1.7) months. Both cross-sectional and longitudinal differences in lesion distribution between RRMS and SPMS patients were analyzed with lesion probability maps (LPMs) and permutation-based inference. Results: MS lesions clustered around the lateral ventricles and in the centrum semiovale. Cross-sectionally, compared to RRMS patients, the SPMS patients showed a significantly higher regional probability of T1 hypointense lesions ( p≤0.03) in the callosal body, the corticospinal tract, and other tracts adjacent to the lateral ventricles, but not of T2 lesions (peak probabilities were RRMS: T1 9%, T2 18%; SPMS: T1 21%, T2 27%). No longitudinal changes of regional T1 and T2 lesion volumes between baseline and follow-up scan were found. Conclusion: The results suggest a particular vulnerability to neurodegeneration during disease progression in a number of WM tracts.

T1 relaxation maps allow differentiation between pathologic tissue subsets in relapsing-remitting and secondary progressive multiple sclerosis

2004 ◽  
Vol 10 (5) ◽  
pp. 556-561 ◽  
Author(s):  
A Castriota-Scanderbeg ◽  
F Fasano ◽  
M Filippi ◽  
C Caltagirone
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Relaxation Times ◽  
Brain Regions ◽  
Progressive Multiple Sclerosis ◽  
Clinical Group ◽  
Secondary Progressive ◽  
Normal Appearing White Matter ◽  
Relapsing Remitting ◽  
Normal White Matter

In an attempt to clarify whether T1 relaxation time mapping may assist in characterizing the pathological brain tissue substrate of multiple sclerosis (MS), we compared the T1 relaxation times of lesions, areas of normal-appearing white matter (NAWM) located proximal to lesions, and areas of NAWM located distant from lesions in 12 patients with the relapsing-remitting and 12 with the secondary progressive (SP) subtype of disease. Nine healthy volunteers served as controls. Calculated mean T1 values were averaged across all patients within each clinical group, and comparisons were made by means of the Mann-Whitney U-test. Significant differences were found between all investigated brain regions within each clinical subgroup. Significant differences were also detected for each investigated brain region among clinical subgroups. While T1 values of NAWM were significantly higher in patients with SP disease than in normal white matter (NWM) of controls, no differences were detected when corresponding brain areas of patients with RR MS were compared with NWM of controls. T1 maps identify areas of the brain that are damaged to a different extent in patients with MS, and may be of help in monitoring disease progression.

Effect of drugs in secondary disease progression in patients with multiple sclerosis

2004 ◽  
Vol 10 (3_suppl) ◽  
pp. S46-S55 ◽  
Author(s):  
Ludwig Kappos
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Progressive Multiple Sclerosis ◽  
Positive Effects ◽  
Secondary Progressive ◽  
The North ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Effect Of Therapy ◽  
Almost All

Secondary progressive multiple sclerosis (SPMS) is a form of MS characterized by continuously worsening disability with or without superimposed relapses that occurs after a variable period of relapsing remitting disease and results in limited ambulation for almost all patients. The use of interferon beta (IFN b) for immunomodulation in patients with SPMS has been evaluated in four recent clinical trials: The European multicentre trial on IFN b-1b in SPMS (EUSPMS), the Secondary Progressive Efficacy Trial of Rebif (IFN b-1a) in MS (SPEC TRIMS), the North A merican Study of IFN b-1b in SPMS (NA SPMS), and the Internatio nal MS Secondary Progressive Avonex C linical Trial (IMPAC T). EUSPMS was the only trial to demonstrate a significant positive effect of therapy on disease progression as measured by the expanded disability status scale (EDSS). However, results from all studies demonstrated significant positive effects of treatment on relapse, T2 lesion load, and gadolinium enhancement. Immunomodulation with IFN b has the potential to significantly slow disease progression and improve quality of life for patients with SPMS. While results with monthly IV Ig were disappointing, positive effects on disease progression have been reported with the applicatio n of immunosuppressants, especially Mitoxantrone. The risk-benefit ratio of these cytostatic agents remains controversial. New strategies addressing the important neurodegenerative aspects of the disease are urgently needed.

Prevalence of multiple sclerosis in Sardinia: A systematic cross-sectional multi-source survey

2019 ◽  
Vol 26 (3) ◽  
pp. 372-380 ◽  
Author(s):  
Silvana AM Urru ◽  
Antonello Antonelli ◽  
Giuseppe M Sechi ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Health Interventions ◽  
Public Health Interventions ◽  
Cross Sectional ◽  
Mediterranean Populations ◽  
Secondary Progressive ◽  
High Prevalence ◽  
Relapsing Remitting ◽  
Prevalence Estimates ◽  
Study Population

Background: Partial surveys in sub-regions of Sardinia have suggested a high prevalence of multiple sclerosis (MS) on the island, relative to other Mediterranean populations. We assessed the island-wide prevalence of MS and its detailed distribution in Sardinia. Methods: The study population consisted of 5677 MS patients, 1735 men and 3942 women, living in Sardinia. Neurologists retrospectively examined electronic and paper-based records of patients with a diagnosis of MS. The data were then linked to the administrative health information systems. Crude, age-, and sex-specific prevalence estimates of disease were calculated. Results: The overall age-adjusted MS prevalence was 330 per 100,000 (95% confidence interval (CI) 321–338) in individuals older than 15 years, 447 in women (95% CI 433–461), and 205 in men (95% CI 195–214). The prevalence was highest in the Ogliastra and Nuoro districts, respectively, 425 (95% CI 372–478) and 419 (95% CI 387–451), and lowest in the Olbia-Tempio district, 217 (95% CI 195–239). Most cases had relapsing–remitting MS (79.3%), 16.3% had secondary-progressive MS, and 4.4% had primary-progressive MS. Conclusion: These prevalence are among the highest reported so far worldwide. They provide estimates for comparative analyses in other populations and are essential for public health interventions.

scholarly journals 7 T imaging reveals a gradient in spinal cord lesion distribution in multiple sclerosis

Brain ◽  
2020 ◽  
Vol 143 (10) ◽  
pp. 2973-2987 ◽  
Author(s):  
Russell Ouellette ◽  
Constantina A Treaba ◽  
Tobias Granberg ◽  
Elena Herranz ◽  
Valeria Barletta ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
White Matter ◽  
Cervical Spinal Cord ◽  
White Matter Lesions ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Spinal Cord Lesions ◽  
Secondary Progressive ◽  
Relapsing Remitting

Abstract We used 7 T MRI to: (i) characterize the grey and white matter pathology in the cervical spinal cord of patients with early relapsing-remitting and secondary progressive multiple sclerosis; (ii) assess the spinal cord lesion spatial distribution and the hypothesis of an outside-in pathological process possibly driven by CSF-mediated immune cytotoxic factors; and (iii) evaluate the association of spinal cord pathology with brain burden and its contribution to neurological disability. We prospectively recruited 20 relapsing-remitting, 15 secondary progressive multiple sclerosis participants and 11 age-matched healthy control subjects to undergo 7 T imaging of the cervical spinal cord and brain as well as conventional 3 T brain acquisition. Cervical spinal cord imaging at 7 T was used to segment grey and white matter, including lesions therein. Brain imaging at 7 T was used to segment cortical and white matter lesions and 3 T imaging for cortical thickness estimation. Cervical spinal cord lesions were mapped voxel-wise as a function of distance from the inner central canal CSF pool to the outer subpial surface. Similarly, brain white matter lesions were mapped voxel-wise as a function of distance from the ventricular system. Subjects with relapsing-remitting multiple sclerosis showed a greater predominance of spinal cord lesions nearer the outer subpial surface compared to secondary progressive cases. Inversely, secondary progressive participants presented with more centrally located lesions. Within the brain, there was a strong gradient of lesion formation nearest the ventricular system that was most evident in participants with secondary progressive multiple sclerosis. Lesion fractions within the spinal cord grey and white matter were related to the lesion fraction in cerebral white matter. Cortical thinning was the primary determinant of the Expanded Disability Status Scale, white matter lesion fractions in the spinal cord and brain of the 9-Hole Peg Test and cortical thickness and spinal cord grey matter cross-sectional area of the Timed 25-Foot Walk. Spinal cord lesions were localized nearest the subpial surfaces for those with relapsing-remitting and the central canal CSF surface in progressive disease, possibly implying CSF-mediated pathogenic mechanisms in lesion development that may differ between multiple sclerosis subtypes. These findings show that spinal cord lesions involve both grey and white matter from the early multiple sclerosis stages and occur mostly independent from brain pathology. Despite the prevalence of cervical spinal cord lesions and atrophy, brain pathology seems more strongly related to physical disability as measured by the Expanded Disability Status Scale.

White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis

2016 ◽  
Vol 22 (11) ◽  
pp. 1429-1437 ◽  
Author(s):  
Kim A Meijer ◽  
Nils Muhlert ◽  
Mara Cercignani ◽  
Varun Sethi ◽  
Maria A Ron ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Cognitive Domains ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Tract Damage

Background: While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind. Objective: The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients. Methods: Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS). Results: A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance ( R2 = 0.48, p = 0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major. Conclusion: Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patients.

scholarly journals Elevated sCD40L in Secondary Progressive Multiple Sclerosis in Comparison to Non-progressive Benign and Relapsing Remitting Multiple Sclerosis

2021 ◽  
Vol 13 ◽  
pp. 117957352110507
Author(s):  
Qi Wu ◽  
Qin Wang ◽  
Jennifer Yang ◽  
Jacob WS Martens ◽  
Elizabeth A Mills ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Plasma Levels ◽  
Disease Onset ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background: The long-term prognosis of relapsing-remitting multiple sclerosis (RRMS) is usually unfavorable as most patients transition to secondary progressive multiple sclerosis (SPMS) with accumulative disability. A rare form of non-progressive multiple sclerosis (MS) also exists, known as benign MS (BMS or NPMS), which lacks disease progression defined as Expanded Disability Status Scale (EDSS) ≤3 after 15 years of disease onset without treatment. Purpose: Our study aims to identify soluble plasma factors predicting disease progression in multiple sclerosis (MS). Research Design and Study Sample: We utilized Luminex multiplex to analyze plasma levels of 33 soluble factors, comparing 32 SPMS patients to age-, sex-, and disease duration-matched non-progressive BMS patients, as well as to RRMS patients and healthy controls. Results: Plasma levels of EGF, sCD40L, MCP1/CCL2, fractalkine/CX3CL1, IL-13, Eotaxin, TNFβ/LTα, and IL-12p40 were significantly different between the various types of MS. Plasma sCD40L was significantly elevated in SPMS compared to BMS and RRMS. The combination of MCP1/CCL2 and sCD40L discriminated between RRMS and SPMS. MCP1/CCL2 was found to be the most effective classifier between BMS and RRMS, while BMS was most effectively distinguished from SPMS by the combination of sCD40L and IFNγ levels. Conclusions: These differences may facilitate personalized precision medicine and aid in the discovery of new therapeutic targets for disease progression through the improvement of patient stratification.

scholarly journals Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 84 ◽  
Author(s):  
Stephanie Herman ◽  
Torbjörn Åkerfeldt ◽  
Ola Spjuth ◽  
Joachim Burman ◽  
Kim Kultima
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Progression ◽  
High Resolution Mass Spectrometry ◽  
Progressive Multiple Sclerosis ◽  
Pyrimidine Metabolism ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

To better understand the pathophysiological differences between secondary progressive multiple sclerosis (SPMS) and relapsing-remitting multiple sclerosis (RRMS), and to identify potential biomarkers of disease progression, we applied high-resolution mass spectrometry (HRMS) to investigate the metabolome of cerebrospinal fluid (CSF). The biochemical differences were determined using partial least squares discriminant analysis (PLS-DA) and connected to biochemical pathways as well as associated to clinical and radiological measures. Tryptophan metabolism was significantly altered, with perturbed levels of kynurenate, 5-hydroxytryptophan, 5-hydroxyindoleacetate, and N-acetylserotonin in SPMS patients compared with RRMS and controls. SPMS patients had altered kynurenine compared with RRMS patients, and altered indole-3-acetate compared with controls. Regarding the pyrimidine metabolism, SPMS patients had altered levels of uridine and deoxyuridine compared with RRMS and controls, and altered thymine and glutamine compared with RRMS patients. Metabolites from the pyrimidine metabolism were significantly associated with disability, disease activity and brain atrophy, making them of particular interest for understanding the disease mechanisms and as markers of disease progression. Overall, these findings are of importance for the characterization of the molecular pathogenesis of SPMS and support the hypothesis that the CSF metabolome may be used to explore changes that occur in the transition between the RRMS and SPMS pathologies.

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