Low degree of cortical pathology is associated with benign course of multiple sclerosis

2012 ◽  
Vol 19 (7) ◽  
pp. 904-911 ◽  
Author(s):  
Massimiliano Calabrese ◽  
Alice Favaretto ◽  
Valentina Poretto ◽  
Chiara Romualdi ◽  
Francesca Rinaldi ◽  
...  

Background: Although a more favorable course of multiple sclerosis is associated with a low degree of cortical pathology, only longitudinal studies could definitely confirm this association. Materials and Methods: We followed 95 early relapsing–remitting MS (RRMS; median Expanded Disability Status Scale (EDSS) = 1.5, mean disease duration = 3.1 ± 1.3 years) and 45 benign MS patients (EDSS ≤ 3.0, disease duration ≥ 15 years, normal cognition) for 6 years, with EDSS evaluations every 6 months and brain magnetic resonance imaging (MRI) at baseline and then yearly. Results: At baseline, we detected 406 cortical lesions (CLs) in 67/95 (70.5%) early RRMS and in 24/45 (53.3%) benign MS patients ( p = 0.046). After 6 years, the appearance of new CLs was observed in 80/95 (84.2%; 518 CLs) of our early RRMS and in 25/45 (55.5%; 63 CLs; p < 0.001) benign MS patients. At baseline, after corrections for age and disease duration, we observed a cortical thinning of several frontal and temporal regions in our RRMS study patients, compared to the benign MS patients ( p ranging between 0.001–0.05). After 6 years, the cortical thinning had increased significantly in several cortices of RRMS patients, but only in the occipital-temporal ( p = 0.036) and superior parietal gyrus ( p = 0.035) of those with benign MS. Stepwise regression analysis revealed the CL volume ( p = 0.006) and the cortical thickness of the temporal middle ( p < 0.001), insular long ( p < 0.001), superior frontal ( p < 0.001) and middle frontal gyri ( p < 0.001) as the most sensitive independent predictors of a favorable disease course. Conclusions: Our data confirmed that a significantly milder cortical pathology characterizes the most favorable clinical course of MS. Measures of focal and diffuse grey matter should be combined to increase the accuracy in the identification of a benign MS course.

2013 ◽  
Vol 71 (5) ◽  
pp. 275-279 ◽  
Author(s):  
Denis Bernardi Bichuetti ◽  
Enedina Maria Lobato de Oliveira ◽  
Nilton Amorin de Souza ◽  
Mar Tintoré ◽  
Alberto Alain Gabbai

Although neuromyelitis optica (NMO) is known to be a more severe disease than relapsing-remitting multiple sclerosis (RRMS), few studies comparing both conditions in a single center have been done.Methods:Comparison of our previously published cohort of 41 NMO patients with 177 RRMS patients followed in the same center, from 1994 to 2007.Results:Mean age of onset was 32.6 for NMO and 30.2 for RRMS (p=0.2062) with mean disease duration of 7.4 years for NMO and 10.3 years for RRMS. Patients with NMO had a higher annualized relapse rate (1.0 versus 0.8, p=0.0013) and progression index (0.9 versus 0.6, p≪0.0001), with more patients reaching expanded disability status scale (EDSS) 6.0 (39 versus 17%, p=0.0036). The odds ratio for reaching EDSS 6.0 and being deceased due to NMO in comparison to RRMS were, respectively, 3.14 and 12.15.Conclusion:Patients with NMO have a more severe disease than patients with RRMS, including higher risk of dying of a demyelinating disease.


Neurology ◽  
2017 ◽  
Vol 89 (24) ◽  
pp. 2462-2468 ◽  
Author(s):  
Joachim Burman ◽  
Johan Zelano

Objective:To determine the cumulative incidence of epilepsy in a population-based cohort of patients with multiple sclerosis (MS) and to investigate the association between epilepsy and clinical features of MS.Methods:All available patients in the Swedish MS register (n = 14,545) and 3 age- and sex-matched controls per patient randomly selected from the population register (n = 43,635) were included. Data on clinical features of MS were retrieved from the Swedish MS register, and data on epilepsy and death were retrieved from comprehensive patient registers.Results:The cumulative incidence of epilepsy was 3.5% (95% confidence interval [CI] 3.17–3.76) in patients with MS and 1.4% (95% CI 1.30–1.52) in controls (risk ratio 2.5, 95% CI 2.19–2.76). In a Cox proportional model, MS increased the risk of epilepsy (hazard ratio 3.2, 95% CI 2.64–3.94). Patients with relapsing-remitting MS had a cumulative incidence of epilepsy of 2.2% (95% CI 1.88–2.50), whereas patients with progressive disease had a cumulative incidence of 5.5% (95% CI 4.89–6.09). The cumulative incidence rose continuously with increasing disease duration to 5.9% (95% CI 4.90–7.20) in patients with disease duration ≥34 years. Patients with an Expanded Disability Status Scale (EDSS) score ≥7 had a cumulative incidence of epilepsy of 5.3% (95% CI 3.95–7.00). Disease duration and EDSS score were associated with epilepsy after multiple logistic regression (odds ratio [OR] 1.03, 95% CI 1.01–1.04 per year, p = 0.001; and OR 1.2, 95% CI 1.09–1.26 per EDSS step, p < 0.0001).Conclusions:Epilepsy is more common among patients with MS than in the general population, and a diagnosis of MS increases the risk of epilepsy. Our data suggest a direct link between severity of MS and epilepsy.


2021 ◽  
Author(s):  
Amir Valizadeh ◽  
Elham Barati ◽  
Mohammad Ali Sahraian ◽  
Mohammad Reza Fattahi ◽  
Mana Moassefi

Abstract Introduction: As the role of neurodegeneration in the pathophysiology of multiple sclerosis (MS) has become more prominent, the formation and evolution of chronic or persistent T1-hypointense lesions (Black Holes) have been used as markers of axonal loss and neuronal destruction to measure disease activity. However, findings regarding this subject are controversial. In this study we aim to clarify the level of importance of T1 hypointense lesions for estimating the prognosis of patients.Methods: We will search MEDLINE (through PubMed), Embase and Web of Science for relevant studies. We will extract the Spearman's rank correlation coefficient (SRCC) between the T1 hypointense lesion volume and Extended Disability Status Scale (EDSS) in participants. All included studies will be evaluated for the risk of bias. We will also perform a meta-analysis on the data. The risk of publication bias will be evaluated using Funnel plots. Finally, we will assess the confidence in cumulative evidence using an adapted version of GRADE.


2010 ◽  
Vol 16 (11) ◽  
pp. 1341-1348 ◽  
Author(s):  
Bassem Yamout ◽  
Aline Herlopian ◽  
Zeinab Issa ◽  
Robert H Habib ◽  
Ahmad Fawaz ◽  
...  

Background: Extracranial venous stenosis (EVS) has recently been implicated as the primary cause of multiple sclerosis (MS). Objective: The aim of this study was to determine the presence of EVS in MS patients. Methods: We performed selective extracranial venography on 42 patients with early MS (EMS): clinically isolated syndrome (CIS) or relapsing—remitting MS (RRMS) of less than 5 years duration, and late MS (LMS): RRMS of more than 10 years duration. Magnetic resonance imaging (MRI) and clinical relapse data were reviewed for all patients with EVS. Results: EVS was present in 7/29 patients with EMS and 12/13 patients with LMS, a highly significant statistical difference ( p< 0.001). Only 3/42 patients (all in the LMS group) had two vessel stenoses, while the rest had only one vessel involved. EVS was seen in 1/11 patients with CIS compared with 6/18 RRMS patients of less than 5 years duration. Disease duration was greater in patients with EVS overall ( p < 0.005). LMS remained an independent predictor of EVS following multivariate adjustment for gender, age at disease onset and Expanded Disability Status Scale (EDSS) (Adjusted Odds Ratio = 29 (3—298); p = 0.005]. Within the EMS group, patients with ( n = 7) and without ( n = 22) EVS had similar EDSS and disease duration, suggesting similar disease severity. No clear correlation could be found between site of EVS and anatomic localization of either clinical relapses or MRI gadolinium-enhancing lesions. Conclusions: We conclude that EVS is an unlikely cause of MS since it is not present in most patients early in the disease and rarely involves more than one extracranial vein. It is likely to be a late secondary phenomenon.


2008 ◽  
Vol 14 (5) ◽  
pp. 663-670 ◽  
Author(s):  
T Vollmer ◽  
H Panitch ◽  
A Bar-Or ◽  
J Dunn ◽  
MS Freedman ◽  
...  

Forty relapsing multiple sclerosis patients with 1–15 gadolinium (Gd)-enhancing lesions on screening brain magnetic resonance imaging (MRI) and Expanded Disability Status Scale (EDSS) scores 0–6.5 were randomized to receive short-term induction therapy with mitoxantrone (three monthly 12 mg/m2 infusions) followed by 12 months of daily glatiramer acetate (GA) therapy 20 mg/day subcutaneously for a total of 15 months (M-GA, n = 21) or daily GA 20 mg/day for 15 months (GA, n = 19). MRI scans were performed at months 6, 9, 12 and 15. The primary measure of outcome was the incidence of adverse events; secondary measures included number of Gd-enhanced lesions, confirmed relapses and EDSS changes. Except age, baseline demographic characteristics were well matched in both treatment arms. Both treatments were safe and well tolerated. M-GA induction produced an 89% greater reduction (relative risk (RR) = 0.11, 95% confidence interval (CI): 0.04–0.36, p = 0.0001) in the number of Gd-enhancing lesions at months 6 and 9 and a 70% reduction (RR = 0.30, 95% CI: 0.11–0.86, p = 0.0147) at months 12 and 15 versus GA alone. Mean relapse rates were 0.16 and 0.32 in the M-GA and GA groups, respectively. Short-term immunosuppression with mitoxantrone followed by daily GA for up to 15 months was found to be safe and effective, with an early and sustained decrease in MRI disease activity.


Author(s):  
Mohsen Foroughipour ◽  
Sahar Gazeran

Background: Multiple sclerosis (MS) is a neurologic disorder with a considerable global burden. During the last decades, some pharmaceutical treatments have been approved for patients with MS. Dimethyl fumarate (DMF) is one of these drugs which has been reported to have early promising results in recent studies, but the efficacy of this drug in patients with MS is still being studied in different parts of the world. In the present study, we evaluated the effectiveness of DMF therapy on reducing relapses, lesions, and disability in Iranian patients with MS. Methods: The present single-arm before-after study was approved by the Ethics Committee of Mashhad University of Medical Sciences, Mashhad, Iran [Iranian Registry of Clinical Trial (IRCT) code: IRCT20190121042439N1]. Every patient who was diagnosed with relapsing MS was considered eligible to enroll in the present clinical trial. Before receiving DMF therapy, the baseline liver function tests and complete blood count were obtained from all individuals. Also, a baseline brain magnetic resonance imaging (MRI) was obtained and Expanded Disability Status Scale (EDSS) was documented from all patients. After receiving 240 mg DMF twice daily for 12 months, the laboratory and imaging measurements as well as EDSS were repeated. Furthermore, the total number of relapses within the study period was recorded. Satisfaction with DMF treatment was determined by answering a yes-no question. Results: A total number of 50 patients enrolled in the study and most of them were female (80%). There was a significant decrease in EDSS score and gadolinium (GD)-enhancing lesions after the study period (P < 0.001 for each). Moreover, the attacks significantly dropped after the study period (P < 0.001) and 86% of patients were satisfied with their treatment. Conclusion: The findings of this study showed that 240 mg DMF administered twice daily can effectively reduce disability and provide satisfaction within the first year of therapy in patients with MS.


2009 ◽  
Vol 16 (1) ◽  
pp. 45-54 ◽  
Author(s):  
A. Prinster ◽  
M. Quarantelli ◽  
R. Lanzillo ◽  
G. Orefice ◽  
G. Vacca ◽  
...  

Previous studies have shown a preferential loss of grey matter in fronto-temporal regions in patients with multiple sclerosis. Studies of correlates of disease severity are more controversial, because some studies have suggested an association between sensorimotor cortex atrophy and Expanded Disability Status Scale score, while others did not find such a correlation. The objective of this study was to assess the correlation of regional loss of grey matter and white matter with indexes of clinical and radiological severity in relapsing—remitting multiple sclerosis, including the Expanded Disability Status Scale and lesion load. Correlations between Expanded Disability Status Scale, lesion load and disease duration were assessed in 128 patients with relapsing—remitting multiple sclerosis (Expanded Disability Status Scale range 1.0—6.0) using optimized voxel-based morphometry. Bilateral loss of grey matter in sensorimotor cortices was correlated with Expanded Disability Status Scale, and tissue loss also involved adjacent white matter, extending along pyramidal tracts to the brainstem. Increasing lesion load was correlated with loss of deep grey matter and white matter. No specific region of grey matter or white matter showed a significant correlation with disease duration. These findings support the hypothesis that motor neuron involvement plays a major role in the progression of physical disability. Lesion load accrual affects mainly highly interconnected subcortical structures, while disease duration has a less significant impact on brain atrophy, probably owing to the inter-subject heterogeneity of the clinical course of the disease.


2017 ◽  
Vol 25 (1) ◽  
pp. 81-91 ◽  
Author(s):  
John Fleming ◽  
Gianna Hernandez ◽  
Leslie Hartman ◽  
Jane Maksimovic ◽  
Sara Nace ◽  
...  

Background: The hygiene hypothesis suggests that microbial replacement may be therapeutic in allergic and autoimmune diseases. Nevertheless, the results of helminth treatment, including in multiple sclerosis (MS), have been inconclusive. Objective: To assess safety and brain magnetic resonance imaging (MRI) activity in subjects with relapsing-remitting multiple sclerosis (RRMS) during oral administration of ova from the porcine whipworm, Trichuris suis (TSO). Methods: A total of 16 disease-modifying treatment (DMT) naive RRMS subjects were studied in a baseline versus treatment (BVT) controlled prospective study. MRI scans were performed during 5 months of screening-observation, 10 months of treatment, and 4 months of post-treatment surveillance. Results: No serious symptoms or adverse events occurred during treatment. For the cohort, there was a trend consistent with a 35% diminution in active lesions when observation MRIs were compared to treatment MRIs ( p = 0.08), and at the level of individuals, 12 of 16 subjects improved during TSO treatment. T regulatory lymphocytes were increased during TSO treatment. Conclusion: TSO is safe in RRMS subjects. Potentially favorable MRI outcomes and immunoregulatory changes were observed during TSO treatment; however, the magnitude of these effects was modest, and there was considerable variation among the responses of individual subjects.


2003 ◽  
Vol 9 (1) ◽  
pp. 36-38 ◽  
Author(s):  
Hossein Kalanie ◽  
Kurosh Gharagozli ◽  
Amir Reza Kalanie

C linical findings of 200 patients in Iran with definite multiple sclerosis (MS) according to Poser et al.’s criteria and positive findings on magnetic resonance imaging (MRI) have been reviewed. The clinical course was relapsing-remitting (RR) for 88%, primary progressive (PP) for 7% and secondary progressive (SP) for 5% of cases. The mean age of onset was 27±7.4 years for the whole group and 37.1±8.8 years for PPMS. The gender ratio was 2.5:1 female:male. Involvement of the pyramidal system was the most common mode of presentation. Five per cent of patients had positive family history for the disease, 14% of patients had benign MS and 12% with disease duration longer than five years had an Expanded Disability Status Scale-2. The optico-spinal form was not a common form of presentation in the group.


2002 ◽  
Vol 8 (6) ◽  
pp. 447-451 ◽  
Author(s):  
T Seifert ◽  
B C Kieseier ◽  
S Ropele ◽  
S Strasser-Fuchs ◽  
F Quehenberger ◽  
...  

Tumor necrosis factor-a (TNF-a) is involved in the pathogenesis of multiple sclerosis (MS). It has to be released from its cell membrane-bound precursor by proteolytic cleavage. This is mainly performed by a member of the ADAM (a disintegrin and metalloproteinase) family of enzymes, TNF-a-converting enzyme (TACE, ADAM 17). In a longitudinal study on 11 relapsing-remitting MS patients, we qualitatively determined mRNA expression of TNF-a and TACE in peripheral blood mononuclear cells (PBMCs) without ex vivo stimulation. mRNA expression was related to disease activity as assessed by monthly gadolinium (Gd)-enhanced brain magnetic resonance imaging (MRI). Patients found positive for TACE mRNA in PBMCs showed a significantly higher mean number of new Gd-enhancing lesions per scan one month following PBMC sampling.


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