Defining brain volume cutoffs to identify clinically relevant atrophy in RRMS

Objective: To define values of normalized brain volume (NBV) that can be categorized as low, medium, or high, according to baseline characteristics of relapsing-remitting multiple sclerosis (RRMS) patients. Methods: Expected NBV (eNBV) was calculated for each patient based on age, disease duration, sex, baseline Expanded Disability Status Scale (EDSS), and T2-lesion volume, entering these variables into a multiple regression model run on 2342 RRMS patients (pooled FREEDOMS/FREEDOMS-II population). According to the difference between their observed NBV and their eNBV, patients were classified as having low NBV, medium NBV, or high NBV. We evaluated whether these NBV categories were clinically meaningful by assessing correlation with disability worsening. Results: The distribution of differences between observed NBV and eNBV was used to categorize patients as having low NBV, medium NBV or high NBV. Taking the high-NBV group as reference, the hazard ratios (HRs) for 2-year disability worsening, adjusted for treatment effect, were 1.23 (95% confidence interval (CI): 0.92–1.63, p = 0.16) for the medium NBV and 1.75 (95% CI: 1.26–2.44, p = 0.001) for the low NBV. The predictive value of NBV groups was preserved over 4 years. Treatment effect appeared more evident in low-NBV patients (HR = 0.58) than in medium-NBV (HR = 0.72) and in high-NBV (HR = 0.80) patients; however, the difference was not significant ( p = 0.57). Conclusion: RRMS patients can be categorized into disability risk groups based on individual eNBV values according to baseline demographics and clinical characteristics.

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Validating the use of brain volume cutoffs to identify clinically relevant atrophy in RRMS

Multiple Sclerosis Journal ◽

10.1177/1352458517743804 ◽

2017 ◽

Vol 25 (2) ◽

pp. 217-223 ◽

Cited By ~ 1

Author(s):

Francesca Bovis ◽

Nicola De Stefano ◽

Joshua R Steinerman ◽

Volker Knappertz ◽

Maria Pia Sormani

Keyword(s):

Brain Volume ◽

Phase Iii ◽

Prognostic Impact ◽

Two Phase ◽

Data Set ◽

Phase Iii Clinical Trials ◽

Hazard Ratios ◽

Baseline Variable ◽

The Difference ◽

Relapsing Remitting Multiple Sclerosis

Background: Baseline brain volume (BV) is predictive at a group level but is difficult to interpret at the single patient level. Objective: To validate BV cutoffs able to identify clinically relevant atrophy in relapsing–remitting multiple sclerosis (RRMS) patients. Methods: The expected normalized brain volume (NBV) for each patient was calculated using RRMS patients from two phase III clinical trials, applying a linear formula developed on the baseline variable of an independent data set. The difference between these expected NBV values and those actually observed was calculated and used to categorize the patients in the low-NBV, medium-NBV, and high-NBV groups. Results: The 2-year probability of 3-month confirmed disability worsening was significantly associated with the NBV categorization ( p = 0.006), after adjusting for treatment effect. Taking the high-NBV group as a reference, the hazard ratios for the medium-NBV and low-NBV groups were 1.22 (95% confidence interval (CI): 0.85–1.76, p = 0.27) and 1.69 (95% CI: 1.11–2.57, p = 0.01), respectively. Conclusion: This study validates the use of BV cutoffs to identify clinically relevant atrophy in RRMS study by showing that the three groups classified according to the baseline NBV adjusted for the other prognostic variables have a significant prognostic impact on the risk of disability progression.

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Pilot Study of Minocycline in Relapsing-Remitting Multiple Sclerosis

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100008611 ◽

2008 ◽

Vol 35 (2) ◽

pp. 185-191 ◽

Cited By ~ 41

Author(s):

Yunyan Zhang ◽

Luanne M Metz ◽

V Wee Yong ◽

Robert B Bell ◽

Michael Yeung ◽

...

Keyword(s):

Multiple Sclerosis ◽

Brain Volume ◽

Small Sample ◽

Control Group ◽

Lesion Volume ◽

Clinical Assessments ◽

Minocycline Treatment ◽

Relapsing Remitting ◽

Relapsing Remitting Multiple Sclerosis ◽

Three Tesla

Background:Current multiple sclerosis (MS) treatment is only partially effective and not all patients respond well. The goal in this study was to evaluate minocycline for its safety, tolerability, and MRI impact as a potential therapy over 36 months after a three month run-in in ten relapsing-remitting (RR) MS patients.Methods:Clinical assessments were at three month intervals until six months, then at six month intervals. Three Tesla MRI was performed monthly during the run-in and first six months of treatment, then at 12, 24, and 36 months.Results:Treatment was safe and well tolerated. Annualized relapse rate was 1.2 during the run-in and 0.25 during treatment. The proportion of active scans was lower during the first six months of treatment (5.6%, p<0.001) and during the extension (8.7%, p= 0.002) than during the run-in (47.5%). Consistent with these outcomes, mean T2 lesion volume remained stable over three years and percent brain volume change was reduced during year three (-0.37%) of minocycline treatment.Conclusions:This trial is limited by small sample and no control group but suggests that minocycline is safe and potentially beneficial in RRMS. This supports further investigation of its efficacy.

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Relationship between Expanded Disability Status Scale scores and the presence of temporomandibular disorders in patients with multiple sclerosis

European Journal of Dentistry ◽

10.4103/ejd.ejd_91_17 ◽

2018 ◽

Vol 12 (01) ◽

pp. 144-148 ◽

Cited By ~ 2

Author(s):

Lucas Senra Correa Carvalho ◽

Osvaldo José Moreira Nascimento ◽

Luciane Lacerda Franco Rocha Rodrigues ◽

Andre Palma Da Cunha Matta

Keyword(s):

Multiple Sclerosis ◽

Temporomandibular Disorders ◽

Control Group ◽

Expanded Disability Status Scale ◽

Exact Test ◽

Disability Status ◽

Relapsing Remitting ◽

Scale Scores ◽

Axis I ◽

Relapsing Remitting Multiple Sclerosis

ABSTRACTObjectives: The objectives of this study were to assess the prevalence of temporomandibular disorders (TMDs) in patients with relapsing-remitting multiple sclerosis (MS) and to investigate whether an association exists between the presence of TMD symptoms and the degree of MS-related disability. Materials and Methods: In all, 120 individuals were evaluated: 60 patients with a diagnosis of relapsing-remitting MS and 60 age- and sex-matched controls without neurological impairments. A questionnaire recommended by the European Academy of Craniomandibular Disorders for the assessment of TMD symptoms was administered. For those who answered affirmatively to at least one of the questions, the RDC/TMD Axis I instrument was used for a possible classification of TMD subtypes. The Expanded Disability Status Scale (EDSS) was the measure of the degree of MS-related disability. Statistical Analysis Used: Fisher’s exact test was used to analyze the data. ANOVA was used to detect significant differences between means and to assess whether the factors influenced any of the dependent variables by comparing means from the different groups. Results: The prevalence of TMD symptoms in patients with MS was 61.7% versus 18.3% in the control group (CG). A diagnosis of TMD was established for 36.7% in the MS group and 3.3% in the CG (P = 0.0001). There were statistically significant differences between degrees of MS-related disability and the prevalence of TMD (P = 0.0288). Conclusions: The prevalence of both TMD and TMD symptoms was significantly greater in the MS group. EDSS scores and TMD prevalence rates were inversely related.

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Assessment of Biochemical and Densitometric Markers of Calcium-Phosphate Metabolism in the Groups of Patients with Multiple Sclerosis Selected due to the Serum Level of Vitamin D3

BioMed Research International ◽

10.1155/2018/9329123 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Natalia Niedziela ◽

Krystyna Pierzchała ◽

Jolanta Zalejska-Fiolka ◽

Jacek T. Niedziela ◽

Ewa Romuk ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Calcium Phosphate ◽

Serum Level ◽

Clinical Stage ◽

Phosphate Metabolism ◽

Disability Status ◽

Relapsing Remitting ◽

Relapsing Remitting Multiple Sclerosis ◽

Calcium Phosphate Metabolism

Background. In addition to the widely known effect of vitamin D3 (vitD3) on the skeleton, its role in the regulation of the immune response was also confirmed. Aim. The assessment of biochemical and densitometric markers of calcium-phosphate metabolism in the groups of patients with relapsing-remitting multiple sclerosis (RRMS) selected due to the serum level of vitamin D3. Methods. The concentrations of biochemical markers and indices of lumbar spine bone densitometry (DXA) were determined in 82 patients divided into vitamin D3 deficiency (VitDd), insufficiency (VitDi), and normal vitamin D3 level (VitDn) subgroups. Results. The highest level of the parathyroid hormone (PTH) and the highest prevalence of hypophosphatemia and osteopenia were demonstrated in VitDd group compared to VitDi and VitDn. However, in VitDd, VitDi, and VitDn subgroups no significant differences were observed in the levels of alkaline phosphatase (ALP) and ionized calcium (Ca2+) and in DXA indices. A negative correlation was observed between the level of vitamin D3 and the Expanded Disability Status Scale (EDSS) in the whole MS group. The subgroups were significantly different with respect to the EDSS scores and the frequency of complaints related to walking according to the EQ-5D. Conclusions. It is necessary to assess calcium-phosphate metabolism and supplementation of vitamin D3 in RRMS patients. The higher the clinical stage of the disease assessed with the EDSS, the lower the level of vitamin D3 in blood serum. Subjectively reported complaints related to difficulties with walking were reflected in the EDSS in VitDd patients.

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

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20130020 ◽

2013 ◽

Vol 71 (5) ◽

pp. 275-279 ◽

Cited By ~ 15

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.

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Epigallocatechin Gallate in Relapsing-Remitting Multiple Sclerosis

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000981 ◽

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.

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Effect of lateral therapy switches to oral moderate-efficacy drugs in multiple sclerosis: a nationwide cohort study

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-324869 ◽

2021 ◽

pp. jnnp-2020-324869 ◽

Cited By ~ 1

Author(s):

Mathias Due Buron ◽

Tomas Kalincik ◽

Finn Sellebjerg ◽

Per Soelberg Sørensen ◽

Melinda Magyari

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Absolute Risk ◽

Dimethyl Fumarate ◽

Interferon Β ◽

First Line ◽

Disease Modifying Therapies ◽

Disability Status ◽

Relapsing Remitting ◽

Relapsing Remitting Multiple Sclerosis

BackgroundSwitching between first-line disease-modifying therapies in patients with clinically stable relapsing–remitting multiple sclerosis (RRMS) due to reasons other than disease activity is frequent, but evidence on the effect of this practice is limited. We investigated the effect of switching patients with stable RRMS on occurrences of disability accumulation, relapses and future treatment discontinuation.MethodsUsing the Danish Multiple Sclerosis Registry, we identified patients with RRMS without disease activity who either (1) stayed on injectable platform therapy (interferon-β or glatiramer acetate) or (2) switched to dimethyl fumarate (DMF) or teriflunomide (TFL) and compared treatment outcomes using propensity-score-based methods and marginal structural models (MSM).ResultsWe included 3206 patients in the study. We found no change in risk of 6-month confirmed Expanded Disability Status Scale score worsening in patients switching to DMF (HR: 1.15, 95% CI 0.88 to 1.50) or TFL (HR: 1.16, 95% CI 0.92 to 1.46). The risk of suffering any relapse tended to decrease when switching to DMF (HR: 0.73, 95% CI 0.51 to 1.04) and tended to increase when switching to TFL (HR: 1.25, 95% CI 0.96 to 1.63). Absolute risk differences were small. MSM analyses showed similar results but did not find an increased relapse risk in TFL switchers.ConclusionSwitching from injectable platform therapies to oral first-line therapies in patients with clinically stable RRMS does not increase the risk of disability accumulation. While the postswitch risk of relapses trended towards marginally higher on TFL, this trend was eliminated by adjustment for time-variant confounders.

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Switching to ocrelizumab in RRMS patients at risk of PML previously treated with extended interval dosing of natalizumab

Multiple Sclerosis Journal ◽

10.1177/1352458520946017 ◽

2020 ◽

pp. 135245852094601

Author(s):

Chiara Rosa Mancinelli ◽

Cristina Scarpazza ◽

Cinzia Cordioli ◽

Nicola De Rossi ◽

Sarah Rasia ◽

...

Keyword(s):

At Risk ◽

Resonance Imaging ◽

Disability Status ◽

Relapsing Remitting ◽

Patients At Risk ◽

Risk Of Disease ◽

Previously Treated ◽

Disease Reactivation ◽

Magnetic Resonance Imaging Mri ◽

Relapsing Remitting Multiple Sclerosis

Discontinuation of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) at risk of progressive multifocal leukoencephalopathy (PML) is associated with disease reactivation. Forty-two RRMS patients, who switched from an extended interval dose (EID) of natalizumab to ocrelizumab, underwent magnetic resonance imaging (MRI) and clinical monitoring during washout and after ocrelizumab starting. During the first 3 months, disease reactivation was observed in five (12%) patients; 6 months after ocrelizumab starting, no further relapses were recorded, and Expanded Disability Status Scale (EDSS) remained stable in 38 (90%) patients. In conclusion, ocrelizumab could be considered a choice to mitigate the risk of disease reactivation in patients previously treated with natalizumab-EID.

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Response to interferon-beta therapy in relapsing-remitting multiple sclerosis: a comparison of different clinical criteria

Multiple Sclerosis Journal ◽

10.1191/135248506ms1278oa ◽

2006 ◽

Vol 12 (3) ◽

pp. 281-286 ◽

Cited By ~ 26

Author(s):

E Portaccio ◽

V Zipoli ◽

G Siracusa ◽

S Sorbi ◽

M P Amato

Keyword(s):

Multiple Sclerosis ◽

Relapse Rate ◽

Interferon Beta ◽

Clinical Criteria ◽

Predictors Of Response ◽

Lower Baseline ◽

Disability Status ◽

Relapsing Remitting ◽

One Year ◽

Relapsing Remitting Multiple Sclerosis

We assessed the proportion and potential predictors of response to interferon-beta (IFNβ) therapy in relapsing-remitting (RR) multiple sclerosis (MS) patients, comparing different definitions of response: a) lower relapse rate during therapy compared to the year and the two years before therapy, b) reduction of relapse rate during therapy of at least 30% compared to the two years before therapy, c) no relapse during treatment, d) no progression on the Expanded Disability Status Scale (EDSS). Among 147 RR patients treated for at least one year, 33 received IFNβ-1b subcutaneously (SC) (Betaferon), 59 IFNβ-1a intramuscularly (Avonex) and 55 IFNβ-1a SC (Rebif). Using definitions a), b) and d), 72%, 73% and 73% patients, respectively, were considered responders. Forty-four per cent of our patients were completely relapse free. In the logistic regression model, using definitions a) and b), a higher relapse rate in the two years preceding the therapy turned out to be a significant predictor of response. Considering definition c), lower baseline relapse rate was associated with a more favourable response.

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