In-vivo evidence for stable neuroaxonal damage in the brain of patients with benign multiple sclerosis

2009 ◽  
Vol 15 (7) ◽  
pp. 789-794 ◽  
Author(s):  
B Benedetti ◽  
M Rovaris ◽  
MA Rocca ◽  
D Caputo ◽  
M Zaffaroni ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Axonal Damage ◽  
Lesion Volume ◽  
Hyperintense Lesion ◽  
Disease Evolution ◽  
Clinical Onset ◽  
Relapsing Remitting ◽  
Benign Multiple Sclerosis

Objective The term benign multiple sclerosis (BMS) is referred to patients who have a mild or absent disability several years after disease clinical onset. Axonal damage can be measured in vivo using proton MR spectroscopy (1H-MRS). In this study, we quantified the severity of “global” axonal damage in BMS and early relapsing–remitting (RR) MS patients, using whole brain N-acetylaspartate (WBNAA) 1H-MRS, to better elucidate the structural correlates of a non-disabling disease evolution. Methods WBNAA concentration was measured in 37 patients with BMS (mean disease duration 22.3 years) and 17 patients with early RRMS (mean disease duration 4.0 years), using an unlocalized 1H-MRS sequence. Dual echo and T1-weighted scans were also obtained to measure T2-hyperintense lesion volume (TLV) and normalized brain volume (NBV). Results TLV was higher in BMS (mean TLV = 13.1 mL) than in early RRMS patients (mean TLV = 7.2 mL) ( P = 0.018), whereas neither NBV (mean NBV: 1491.0 mL in BMS vs 1520.3 mL in RRMS) nor WBNAA concentration (mean WBNAA: 10.5 mmol in BMS vs 11.4 mmol in RRMS) significantly differed between the two groups. In MS patients, no correlation was found between WBNAA concentration and Expanded Disability Status Scale (EDSS), TLV and NBV. Conclusions The similar WBNAA concentrations seen in BMS and early RRMS patients fit with the notion that a non-disabling long-term evolution of MS may be due, at least in part, to non-progression of pathology. Such a condition seems to be independent from MRI-visible lesions burden.

Benign multiple sclerosis in Crete

2010 ◽  
Vol 16 (6) ◽  
pp. 701-706 ◽  
Author(s):  
V. Mastorodemos ◽  
H. Nikolakaki ◽  
M. Tzagournissakis ◽  
D. Kotzamani ◽  
T. Panou ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Background ◽  
Disease Duration ◽  
Age At Onset ◽  
Benign Disease ◽  
Disease Evolution ◽  
Relapsing Remitting ◽  
Benign Multiple Sclerosis ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Our objective was to study multiple sclerosis on Crete, an island of 0.6 million inhabitants sharing a similar genetic background and the same environment. Case ascertainment was achieved using the MS Epidemiology Program Project of Crete. The diagnosis and classification of multiple sclerosis were made by established clinical and magnetic resonance imaging criteria, and disease evolution was assessed by periodic evaluations. Thorough clinical and laboratory evaluations were conducted; a detailed history, including a questionnaire of 36 items, was taken. Data obtained were analysed for possible interaction with disease prognosis. We identified 587 cases of multiple sclerosis (F:M = 1.6), >90% of which were of Cretan origin from both parental lines. Age at onset was 31.5 ± 10.3 years (mean ± SD) and disease duration 12.7 ± 9.1 years. About 84.6% had relapsing remitting multiple sclerosis, 9.4% primary progressive multiple sclerosis and 6% clinically isolated syndrome. Nearly 40% of our multiple sclerosis patients with disease duration >10 years (mean = 16.2 ± 5.3 years) remained with no or mild disability (Expanded Disability Status Scale [EDSS] ≤3). Also, about 30% of patients with relapsing remitting multiple sclerosis showed benign disease evolution (EDSS ≤3) more than 20 years (mean = 24.0 ± 3.3) after onset. Factors predisposing to benign multiple sclerosis included younger age at onset, shorter disease duration and a lower number of relapses. We conclude that a substantial proportion of patients with multiple sclerosis from Crete follow a rather benign disease course, and this may relate to the genetic background of the population and/or to environmental factors.

‘Clinically definite benign multiple sclerosis’, an unwarranted conceptual hodgepodge: evidence from a 30-year observational study

2012 ◽  
Vol 19 (4) ◽  
pp. 458-465 ◽  
Author(s):  
E Leray ◽  
M Coustans ◽  
E Le Page ◽  
J Yaouanq ◽  
J Oger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Observational Study ◽  
Medical Treatments ◽  
Clinical Onset ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Long Term Follow Up ◽  
Benign Multiple Sclerosis ◽  
New Biomarkers

Background: Benign multiple sclerosis (BMS) is a controversial concept which is still debated. However identification of this kind of patients is crucial to prevent them from unnecessary exposure to aggressive and/or long term medical treatments. Objectives: To assess two definitions of ‘clinically definite benign multiple sclerosis’ (CDBMS) using long-term follow-up data, and to look for prognostic factors of CDBMS. Methods: In 874 patients with definite relapsing–remitting MS, followed up for at least 10 years, disability was assessed using the Disability Status Scale (DSS). CDBMS was defined by either DSS score≤2 (CDBMS1 group) or DSS score≤ 3 (CDBMS2 group) at 10 years. We estimated the proportion of patients who were still benign at 20 and 30 years after clinical onset. Results: CDBMS frequency estimates were 57.7% and 73.9% when using CDBMS1 and CDBMS2 definitions, respectively. In the CDBMS1 group, only 41.7% (105/252) of cases were still benign 10 years later, and 41.1% (23/56) after an additional decade, while there were 53.8% (162/301) and 59.5% (44/74) respectively in the CDBMS2 group. Conclusions: This 30-year observational study, which is one of the largest published series, indicates that favourable 10-year disability scores of DSS 2 or 3 fail to ensure a long-term benign course of multiple sclerosis. After every decade almost half of the CDBMS were no longer benign. CDBMS, as currently defined, is an unwarranted conceptual hodgepodge. Other criteria using new biomarkers (genetic, biologic or MRI) should be found to detect benign cases of MS.

T2 hypointensity in the deep gray matter of patients with benign multiple sclerosis

2009 ◽  
Vol 15 (6) ◽  
pp. 678-686 ◽  
Author(s):  
A Ceccarelli ◽  
M Filippi ◽  
M Neema ◽  
A Arora ◽  
P Valsasina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Diffusion Tensor ◽  
Iron Deposition ◽  
Lesion Volume ◽  
Hyperintense Lesion ◽  
Benign Multiple Sclerosis ◽  
Magnetic Resonance Imaging Mri ◽  
Putative Marker ◽  
And Diffusion

Background Gray matter (GM) magnetic resonance imaging (MRI) T2 hypointensity, a putative marker of iron deposition, commonly occurs in multiple sclerosis (MS). However, GM T2 hypointensity in benign MS (BMS) has not yet been characterized. Objective To determine the presence of deep GM T2 hypointensity in BMS, compare it to secondary progressive (SP) MS and assess its association with clinical and diffusion tensor (DT) MRI measures. Methods Thirty-five cognitively unimpaired BMS, 26 SPMS patients, and 25 healthy controls were analyzed for normalized T2-intensity in the basal ganglia and thalamus, global T2 hyperintense lesion volume, global atrophy, and white matter and GM DT metrics. Results BMS and SPMS patients showed deep GM T2 hypointensity compared with controls. T2 hypointensity was similar in both MS subgroups and moderately correlated ( r = −0.45 to 0.42) with DT MRI metrics. GM T2 hypointensity in BMS showed a weak to moderate correlation ( r = −0.44 to −0.35) with disability. Conclusions GM in BMS is not spared from structural change including iron deposition. However, while T2 hypointensity is related to global tissue disruption reflected in DT MRI, the expression of benign versus non-benign MS is likely related to other factors.

scholarly journals Bimonthly Evolution of Cortical Atrophy in Early Relapsing-Remitting Multiple Sclerosis over 2 Years: A Longitudinal Study

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Robert Zivadinov ◽  
Carmen Tekwe ◽  
Niels Bergsland ◽  
Ondrej Dolezal ◽  
Eva Havrdova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Cortical Atrophy ◽  
Lesion Volume ◽  
Disability Progression ◽  
Mixed Effect ◽  
Effect Model ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Late Group

We investigated the evolution of cortical atrophy in patients with early relapsing-remitting (RR) multiple sclerosis (MS) and its association with lesion volume (LV) accumulation and disability progression. 136 of 181 RRMS patients who participated in the Avonex-Steroids-Azathioprine study were assessed bimonthly for clinical and MRI outcomes over 2 years. MS patients with disease duration (DD) at baseline of ≤24 months were classified in the early group (DD of 1.2 years,n=37), while patients with DD > 24 months were classified in the late group (DD of 7.1 years,n=99). Mixed effect model analysis was used to investigate the associations. Significant changes in whole brain volume (WBV) (P<0.001), cortical volume (CV) (P<0.001), and in T2-LV (P<0.001) were detected. No significant MRI percent change differences were detected between early and late DD groups over 2 years, except for increased T2-LV accumulation between baseline and year 2 in the early DD group (P<0.01). No significant associations were found between changes in T2-LV and CV over the followup. Change in CV was related to the disability progression over the 2 years, after adjusting for DD (P=0.01). Significant cortical atrophy, independent of T2-LV accumulation, occurs in early RRMS over 2 years, and it is associated with the disability progression.

Cervical cord magnetization transfer ratio and clinical changes over 18 months in patients with relapsing-remitting multiple sclerosis: a preliminary study

2006 ◽  
Vol 12 (5) ◽  
pp. 662-665 ◽  
Author(s):  
A Charil ◽  
D Caputo ◽  
R Cavarretta ◽  
M P Sormani ◽  
P Ferrante ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Magnetization Transfer ◽  
Small Sample ◽  
Cervical Cord ◽  
Magnetization Transfer Ratio ◽  
Short Term ◽  
Disease Evolution ◽  
Transfer Ratio ◽  
Relapsing Remitting

Background Magnetization transfer ratio (MTR) permits the quantitative estimation of cervical cord tissue damage in patients with multiple sclerosis (MS). Objective To determine whether a single time-point MTR scan of the cervical cord is associated with short-term disease evolution in patients with relapsing-remitting (RR) MS. Methods Using a 1.5-T magnetic resonance imaging (MRI) system with a tailored cervical cord phased array coil, fast short-tau inversion recovery (fast-STIR) and MTR scans were obtained from 14 untreated patients with RRMS at baseline. Cervical cord MTR histograms were derived. Over the 18- month follow-up period, relapse rate was measured and disability assessed by the Expanded Disability Status Scale (EDSS) score. Results Average cervical cord MTR was correlated with relapse rate ( r= -0.56, P = 0.037). A moderate correlation ( r values ranging from -0.33 to -0.36) between baseline cervical cord MTR metrics and EDSS changes over 18 months was also noted, albeit statistical significance was not reached ( P = 0.26 and 0.21, respectively) perhaps because of the relatively small sample size. Conclusions This study suggests that a ‘snapshot’ MT MRI assessment of the cervical cord may detect cervical cord tissue changes associated with short-term disease evolution in RRMS.

Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: Insights from 7 T imaging

2017 ◽  
Vol 24 (11) ◽  
pp. 1433-1444 ◽  
Author(s):  
Céline Louapre ◽  
Sindhuja T Govindarajan ◽  
Costanza Giannì ◽  
Nancy Madigan ◽  
Jacob A Sloane ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Thalamic Lesion ◽  
Cortical Lesions ◽  
Focal Lesions ◽  
Thalamic Degeneration ◽  
Relapsing Remitting ◽  
Thalamic Lesions ◽  
Magnetic Resonance Imaging Mri

Background: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. Objective: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). Methods: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T2* (q-T2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores. We also assessed MS thalamic lesion distribution as a function of distance from CSF. Results: Thalamic lesions were mainly located next to the ventricles. Thalamic volume was decreased in MS versus controls ( p < 10−2); global q-T2* was longer in secondary progressive multiple sclerosis (SPMS) only ( p < 10−2), indicating myelin and/or iron loss. Thalamic atrophy and longer q-T2* correlated with WM lesion volume ( p < 0.01). In relapsing-remitting MS, q-T2* thalamic abnormalities were located next to the WM ( p < 0.01 (uncorrected), p = 0.09 (corrected)), while they were homogeneously distributed in SPMS. Cortical MRI metrics were the strongest predictors of clinical outcome. Conclusion: Heterogeneous pathological processes affect the thalamus in MS. While focal lesions are likely mainly driven by CSF-mediated factors, overall thalamic degeneration develops in association with WM lesions.

scholarly journals Patients with neuromyelitis optica have a more severe disease than patients with relapsingremitting multiple sclerosis, including higher risk of dying of a demyelinating disease

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
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Disease Duration ◽  
Demyelinating Disease ◽  
Age Of Onset ◽  
Severe Disease ◽  
Expanded Disability Status Scale ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

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.

scholarly journals Epigallocatechin Gallate in Relapsing-Remitting Multiple Sclerosis

2021 ◽  
Vol 8 (3) ◽  
pp. e981
Author(s):  
Judith Bellmann-Strobl ◽  
Friedemann Paul ◽  
Jens Wuerfel ◽  
Jan Dörr ◽  
Carmen Infante-Duarte ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Primary Outcome ◽  
Brain Mri ◽  
Trial Registration ◽  
Lesion Volume ◽  
Volume Number ◽  
Egcg Treatment ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo assess the safety and efficacy of epigallocatechin-3-gallate (EGCG) add-on to glatiramer acetate (GA) in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsWe enrolled patients with RRMS (aged 18–60 years, Expanded Disability Status Scale [EDSS] score 0–6.5), receiving stable GA treatment in a multicenter, prospective, double-blind, phase II, randomized controlled trial. Participants received up to 800 mg oral EGCG daily over a period of 18 months. The primary outcome was the proportion of patients without new hyperintense lesions on T2-weighted (T2w) brain MRI within 18 months. Secondary end points included additional MRI and clinical parameters. Immunologic effects of EGCG were investigated in exploratory experiments.ResultsA total of 122 patients on GA were randomly assigned to EGCG treatment (n = 62) or placebo (n = 60). We could not demonstrate a difference between groups after 18 months for the primary outcome or other radiologic (T2w lesion volume, T1w hypointense lesion number or volume, number of cumulative contrast-enhancing lesions, percent brain volume change), or clinical (EDSS, MS functional composite, and annualized relapse rate) parameter. EGCG treatment did not affect immune response to GA. Pharmacologic analysis revealed wide ranging EGCG plasma levels. The treatment was well tolerated with a similar incidence of mostly mild adverse events similar in both groups.ConclusionIn RRMS, oral EGCG add-on to GA was not superior to placebo in influencing MRI and clinical disease activity over 18 months. The treatment was safe at a daily dosage up to 800 mg EGCG. It did not influence immune parameters, despite indication of EGCG being bioavailable in patients.Classification of EvidenceThis study provides Class II evidence that for patients with RRMS, EGCG added to GA did not significantly affect the development of new hyperintense lesions on T2-weighted brain MRI.Trial Registration InformationClinical trial registration number: NCT00525668.

Investigation of outer cortical magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups

2014 ◽  
Vol 20 (10) ◽  
pp. 1322-1330 ◽  
Author(s):  
Rebecca S Samson ◽  
Manuel J Cardoso ◽  
Nils Muhlert ◽  
Varun Sethi ◽  
Claudia AM Wheeler-Kingshott ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Three Dimensional ◽  
Neuronal Loss ◽  
Magnetisation Transfer ◽  
Magnetisation Transfer Ratio ◽  
Outer Cortex ◽  
Transfer Ratio ◽  
Relapsing Remitting ◽  
Healthy Control

Background: Pathological abnormalities including demyelination and neuronal loss are reported in the outer cortex in multiple sclerosis (MS). Objective: We investigated for in vivo evidence of outer cortical abnormalities by measuring the magnetisation transfer ratio (MTR) in MS patients of different subgroups. Methods: Forty-four relapsing–remitting (RR) (mean age 41.9 years, median Expanded Disability Status Scale (EDSS) 2.0), 25 secondary progressive (SP) (54.1 years, EDSS 6.5) and 19 primary progressive (PP) (53.1 years, EDSS 6.0) MS patients and 35 healthy control subjects (mean age 39.2 years) were studied. Three-dimensional (3D) 1×1×1mm3 T1-weighted images and MTR data were acquired. The cortex was segmented, then subdivided into outer and inner bands, and MTR values were calculated for each band. Results: In a pairwise analysis, mean outer cortical MTR was lower than mean inner cortical MTR in all MS groups and controls ( p<0.001). Compared with controls, outer cortical MTR was decreased in SPMS ( p<0.001) and RRMS ( p<0.01), but not PPMS. Outer cortical MTR was lower in SPMS than PPMS ( p<0.01) and RRMS ( p<0.01). Conclusions: Lower outer than inner cortical MTR in healthy controls may reflect differences in myelin content. The lowest outer cortical MTR was seen in SPMS and is consistent with more extensive outer cortical (including subpial) pathology, such as demyelination and neuronal loss, as observed in post-mortem studies of SPMS patients.

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