‘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.

Long-term (up to 22 years), open-label, compassionate-use study of glatiramer acetate in relapsing—remitting multiple sclerosis

2008 ◽  
Vol 14 (4) ◽  
pp. 494-499 ◽  
Author(s):  
Aaron Miller ◽  
Vincent Spada ◽  
Dorothy Beerkircher ◽  
Rivka Riven Kreitman
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Glatiramer Acetate ◽  
Open Label ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Pretreatment Score

To evaluate the safety and efficacy of long-term glatiramer acetate (GA) therapy, 46 patients with relapsing—remitting multiple sclerosis (RRMS) were treated for up to 22 years in an ongoing, open-label study. Kurtzke expanded disability status scale (EDSS) was measured every six months, relapses were reported at occurrence and patients self-reported adverse events (AEs). At GA initiation, disease durations ranged from 0—20 years (median 6.0 years) and at data cut-off (October 2004), GA therapy duration ranged from 1—22 years (median 12.0 years). Mean EDSS score increased 0.9 ± 1.9 from the pretreatment score (3.0 ± 1.8; P = 0.076). Only 10/28 (36%) patients with baseline EDSS <4.0 had a last observed value ≥ 4.0 and 8/34 (24%) with entry EDSS < 6.0 reached EDSS ≥ 6.0. A majority (57%) maintained improved or unchanged EDSS scores. Annualized relapse rate decreased to 0.1 ± 0.2 from 2.9 ± 1.4 prestudy ( P < 0.0001). Of the 18 remaining patients in October 2004 (average disease duration 23 years), 17% with baseline EDSS scores < 4.0 reached EDSS ≥ 4.0 and 28% with baseline scores < 6.0 reached EDSS ≥ 6.0. Adverse events were similar to those reported in short-term clinical trials. This study shows a low rate of relapses and EDSS progression in RRMS patients on GA for up to 22 years. Multiple Sclerosis 2008; 14: 494—499. http://msj.sagepub.com

Late-onset and young-onset relapsing-remitting multiple sclerosis: evidence from a retrospective long-term follow-up study

2018 ◽  
Vol 25 (12) ◽  
pp. 1425-1431 ◽  
Author(s):  
E. D'Amico ◽  
F. Patti ◽  
A. Zanghì ◽  
C. G. Chisari ◽  
S. Lo Fermo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Young Onset ◽  
Follow Up Study ◽  
Relapsing Remitting ◽  
Long Term Follow Up ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

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.

Glatiramer acetate (Copaxone): comparison of continuous versus delayed therapy in a six-year organized multiple sclerosis trial

2003 ◽  
Vol 9 (6) ◽  
pp. 585-591 ◽  
Author(s):  
K P Johnson ◽  
B R Brooks ◽  
C C Ford ◽  
A D Goodman ◽  
R P Lisak ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Neurological Improvement ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Neurologic Disability

The aim of this study was to assess the long-term safety and efficacy of glatiramer acetate (GA) for patients with multiple sclerosis (MS) who received active treatment versus those on placebo for approximately 30 months (24-35 months) before receiving GA during a six-year organized, prospective open label study. Entry required two relapses in the previous two years and an Expanded Disability Status Scale (EDSS) score of 0-5. Patients (251) were equally randomized to daily subcutaneous G A, 20 mg, or to placebo. A fter approximately 30 months, 208 patients continued in an open label study: 101 continued on G A and 107 switched from placebo to active drug. Groups were well matched at randomization and entry to the open label study. Patients always on G A showed a steady decline in relapses: a mean of 1.5 per year at entry, a mean of 0.42 over the entire six years (95% C I=0.34-0.51), a 72% reductio n (P =0.0001). They averaged a relapse every four+ years (yearly rate 0.23 in year six) and 26/101 remain relapse free. Patients did less well if on placebo for 30 months, but relapses then declined, and by year six the rates were similar. O f patients always on GA, 69% showed neurological improvement of > 1 EDSS steps or remained stable compared with 57% if G A treatment was delayed. O f relapse-free patients always on G A over six years, only three of 26 (11%) were worse by]-1 EDSS steps, whereas nine of 21 (43%) in the placebo/active group were worse (P B-0.03). Disability, measured every six months, showed that the group of patients always on G A was relatively stable over the six years, while the group who received placebo for the first two-and-a-half years did significantly less well. Daily injections of GA were well tolerated. This longest ever organized MS treatment trial shows that delaying therapy with GA increases the risk of neurologic disability, reinforcing the rationale for using G A as a first-line treatment early in the course of relapsing-remitting MS.

Pregnancy in women with MS: Impact on long-term disability accrual in a nationwide Danish Cohort

2021 ◽  
pp. 135245852110577
Author(s):  
Johanna Balslev Andersen ◽  
Malthe Faurschou Wandall-Holm ◽  
Per Kragh Andersen ◽  
Finn Sellebjerg ◽  
Melinda Magyari
Keyword(s):  
Multiple Sclerosis ◽  
Clinically Isolated Syndrome ◽  
Time Dependent ◽  
Disease Course ◽  
Expanded Disability Status Scale ◽  
Cox Models ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Edss Score

Background: Pregnancy is considered to influence the disease course in women with multiple sclerosis (MS). Objective: The aim of this study was to investigate the effect of pregnancy on long-term disability accrual in women with MS. Methods: The Danish Multiple Sclerosis Registry (DMSR) was used to identify women diagnosed with clinically isolated syndrome or relapsing-remitting MS. Cox models with pregnancy as a time-dependent exposure and propensity score (PS) models were used to evaluate time to reach confirmed Expanded Disability Status Scale (EDSS) score of 4 and 6. Results: A total of 425 women became parous and 840 remained nulliparous. When including pregnancy as a time-dependent exposure, a non-significant association with time to reach EDSS 4 (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.61–1.20) and EDSS 6 (HR 0.70, 95% CI 0.40–1.20) was found. Correspondingly, the PS model showed no association with pregnancy on time to reach EDSS 4 (HR 0.85, 95% CI 0.56–1.28). Conclusion: This study concludes that pregnancy does not affect long-term disability accumulation.

Clinical impact of intravenous methylprednisolone in attacks of multiple sclerosis

2004 ◽  
Vol 10 (4) ◽  
pp. 413-416 ◽  
Author(s):  
Carlos Nos ◽  
Jaume Sastre-Garriga ◽  
Cecília Borrlàs ◽  
Jordi Río ◽  
Mar Tintoré ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Acute Attack ◽  
Intravenous Methylprednisolone ◽  
Open Label ◽  
Open Label Study ◽  
Neurological Improvement ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Treatment Objective

Background: Intravenous methylprednisolone (IVMP) has been shown to hasten recovery from attacks of multiple sclerosis (MS) without altering the long term evolution of the condition; however, there is little evidence available to suggest which patients are more likely to benefit from IVMP treatment. Objective: To measure clinical change after IVMP treatment and to identify predictors of good outcome. Methods: Retrospective open-label study of medical records from 51 patients with clinically isolated syndromes or relapsing-remitting MS treated with IVMP for an acute attack (54 attacks). Results: A measurable neurological improvement was observed at one month in 44% of these attacks; the only predictor of Expanded Disability Status Scale (EDSS) change at one month was the severity of the attack. Conclusion: Attack severity predicts good response to IVMP when measured by means of EDSS.

scholarly journals The Toronto Observational Study of Natalizumab in Multiple Sclerosis

2011 ◽  
Vol 38 (3) ◽  
pp. 422-428 ◽  
Author(s):  
Kristen M. Krysko ◽  
Paul W. O'Connor
Keyword(s):  
Multiple Sclerosis ◽  
Observational Study ◽  
Relapse Rate ◽  
Self Report ◽  
Duration Of Treatment ◽  
Disease Modifying Therapy ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Natalizumab Treatment ◽  
Insufficient Response

Background:Natalizumab is indicated for the treatment of relapsing multiple sclerosis (MS) with insufficient response to first-line disease-modifying therapy (DMT). We studied the efficacy of natalizumab for treatment of MS in a single centre observational design.Methods:A retrospective observational study of 146 patients [66% female; mean age 37.4; 72% relapsing remitting MS (RRMS), 28% secondary progressive MS (SPMS)] referred for natalizumab treatment at St. Michael's Hospital MS Clinic between 2007 and August 2009. Data included demographic, clinical (Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR)) and patient self-report measures.Results:The mean duration of treatment was 20 months in those treated with natalizumab and 97% had received prior DMTs. Eighty-three patients (57%) received at least 12 months of natalizumab treatment. In those who received at least 12 months of treatment, baseline ARR and EDSS were 1.6 and 2.7 in RRMS patients versus 1.0 and 5.4 in SPMS with relapses. The ARR decreased with natalizumab treatment to 0.38 (76% reduction, p<0.001) in RRMS versus 0.32 in SPMS patients (68% reduction, p=0.01). There was a treatment associated 11% reduction in EDSS to 2.4 (p=0.04) in RRMS, but no significant change in SPMS. Eighty-five percent of patients reported improved overall quality of life (QOL) and 62% indicated improved energy.Conclusions:There was a major reduction in relapse rate, stabilization in EDSS and improvement in QOL and energy in some patients on natalizumab, all similar to treatment effects in the pivotal trial.

scholarly journals Long Term Clinical Prognostic Factors in Relapsing-Remitting Multiple Sclerosis: Insights from a 10-Year Observational Study

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0158978 ◽  
Author(s):  
Gabriel Bsteh ◽  
Rainer Ehling ◽  
Andreas Lutterotti ◽  
Harald Hegen ◽  
Franziska Di Pauli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Prognostic Factors ◽  
Observational Study ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Long-term survival of patients with multiple sclerosis in West France

2007 ◽  
Vol 13 (7) ◽  
pp. 865-874 ◽  
Author(s):  
E. Leray ◽  
SP Morrissey ◽  
J. Yaouanq ◽  
M. Coustans ◽  
E. Le Page ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
General Population ◽  
Fold Increase ◽  
French Population ◽  
Term Survival ◽  
Survival Probabilities ◽  
Clinical Onset ◽  
Disability Status

In France no data have been published about comparing survival in multiple sclerosis (MS) patients with the general French population. We estimated survival probabilities in MS patients from a major centre for MS in West France. We also compared MS survival with the general population and assessed prognostic parameters. All patients with MS onset after January 1976 and classified as dead or alive on 1 January 2004 were included. One thousand eight-hundred and seventy-nine patients (sex ratio W: M 2.3; relapsing/progressive onset 77.4%/22.6%) fulfilled these criteria, disease duration ranged from one to 28 years. By 2004, 68 patients died (51 due to MS) and the 15 and 25-year survival probabilities were 96% and 88%. Male gender, progressive course (either primary or secondary), polysymptomatic onset, and increased annual relapse rate during the first two years of MS were related to a worse prognosis. After a mean follow-up duration of 12.7 years since clinical onset, MS increased the number of deaths compared with the general population. However taking into account disability status, we found that less disabled MS patients had a better survival and highly disabled patients a worse survival (eight-fold increase of mortality) compared with the French population. Multiple Sclerosis 2007; 13: 865—874. http://msj.sagepub.com

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