Multiple sclerosis-associated retrovirus in early multiple sclerosis: a six-year follow-up of a Sardinian cohort

2006 ◽  
Vol 12 (6) ◽  
pp. 698-703 ◽  
Author(s):  
S Sotgiu ◽  
G Arru ◽  
G Mameli ◽  
C Serra ◽  
M Pugliatti ◽  
...  

The human endogenous retroviruses (HERV)-W family contains an extracellular particle detected in multiple sclerosis (MS) patients and designated as MS-associated retrovirus (MSRV). Through nested RT-PCR assays specific for pol MSRV gene, we preliminary reported that its presence in the cerebrospinal fluid (CSF) of early MS patients could be indicative of a poor prognosis upon a three-year follow-up. In the present clinical study, we enlarged our blind observation up to six years. At study entry, 10 MS patients were MSRV- and eight were MSRV+ in the CSF, both groups having a similar mean age and Expanded Disability Status Scale (EDSS) score. After six year follow-up, the mean EDSS significantly differed between the MSRV- and MSRV+ cohorts (4.3 versus 2.2; P = 0.004), as did the annual relapse rate (0.5 in the MSRV- versus 0.3 in the MSRV+; P = 0.01). Finally, two MSRV- patients entered the progressive phase, whilst none of the MSRV+ group entered this phase, and 9/10 MSRV- versus 2/8 MSRV+ patients were treated with immunomodulatory or immunosuppressive drugs (P = 0.009). In conclusion, we found that the presence of MSRV virions in the CSF at the onset of MS is associated, not only with disability accumulation, but also with a higher rate of clinical re-exacerbations. With the known potential pathogenic effects of MSRV given in the literature, further investigations on MSRV are warranted.

2007 ◽  
Vol 13 (5) ◽  
pp. 626-631 ◽  
Author(s):  
M. Debouverie ◽  
L. Taillandier ◽  
S. Pittion-Vouyovitch ◽  
S. Louis ◽  
H. Vespignani

The objectives of this study were to assess the benefits of 1) mitoxantrone after three years of follow-up and 2) disease-modifying treatment (DMT) after stopping mitoxantrone. A retrospective analysis was performed on 304 patients with active relapsing-remitting (RR) or progressive multiple sclerosis (PMS) who were treated with mitoxantrone. After mitoxantrone therapy, some patients received DMT (interferon-beta or glatiramer acetate) while others did not. The disease course of the two groups was evaluated by the Expanded Disability Status Scale (EDSS) before and after mitoxantrone and then every year for three years. The mean EDSS score at starting mitoxantrone and three years after stopping mitoxantrone respectively, were: 3.3 (1.3) and 3.2 (1.7) for the RRMS patients and 5.9 (1.2) and 6.4 (1.4) for the PMS patients. Before starting mitoxantrone, demographic and clinical parameters of predictive disability were not significantly different between patients who received DMT or not. The variation of EDSS between time of stopping mitoxantrone and three years later was significantly different (+0.9 versus +0.3; P=0.03) for patients with RRMS. We found that mitoxantrone treatment induces stable disease up to two years after discontinuation of mitoxantrone therapy. In the third year, patients without DMT deteriorated. Multiple Sclerosis 2007; 13: 626-631. http://msj.sagepub.com


2016 ◽  
Vol 23 (3) ◽  
pp. 456-463 ◽  
Author(s):  
Suresh Menon ◽  
Feng Zhu ◽  
Afsaneh Shirani ◽  
Joel Oger ◽  
Mark S Freedman ◽  
...  

Objective: To examine disease progression in ‘aggressive’ multiple sclerosis (MS), British Columbia, Canada (1980–2009). Methods: Aggressive (or ‘malignant’) MS was defined as Expanded Disability Status Scale (EDSS) ⩾6 within 5 years from onset. The first EDSS ⩾6 was termed ‘baseline’. Within 2, 3 and 5 years post-baseline, patients were categorized as follows: ‘worsened’ or ‘improved’, relative to baseline EDSS (the remainder exhibited no change or had no new scores). The associations between patient characteristics (sex, relapsing onset/primary progressive, onset age, onset symptoms, disease duration, cumulative prior relapses and baseline EDSS) and worsening in disability were examined longitudinally using logistic regression. Results: Of the 225/4341 (5.2%) aggressive/malignant MS patients, 134 (59.6%) were female, 167 (74.2%) were relapsing onset, 94 (41.8%) had received disease-modifying drugs at some point and the mean follow-up was 8.7 years. The proportion of patients who ‘worsened’ increased from 40.4% to 57.8%, while those who ‘improved’ varied little (range, 8.9%–10.2%). The odds of worsening increased with disease duration (adjusted odds ratio (AOR) = 1.36; 95% confidence interval (CI) = 1.22–1.52) and the presence of primary progressive (vs relapsing-onset) MS (AOR = 1.85; 95% CI = 1.01–3.38). Conclusion: Apart from disease duration and a primary progressive course, no clinically useful associations of subsequent disease worsening in patients with aggressive/malignant MS were identified.


2021 ◽  
pp. 135245852098130
Author(s):  
Izanne Roos ◽  
Emmanuelle Leray ◽  
Federico Frascoli ◽  
Romain Casey ◽  
J William L Brown ◽  
...  

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2–34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3–36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5–65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2–61.5). Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.


2021 ◽  
Vol 3 (3) ◽  
pp. 366-376
Author(s):  
Lorenzo Tonetti ◽  
Federico Camilli ◽  
Sara Giovagnoli ◽  
Vincenzo Natale ◽  
Alessandra Lugaresi

Early multiple sclerosis (MS) predictive markers of disease activity/prognosis have been proposed but are not universally accepted. Aim of this pilot prospective study is to verify whether a peculiar hyperactivity, observed at baseline (T0) in early relapsing-remitting (RR) MS patients, could represent a further prognostic marker. Here we report results collected at T0 and at a 24-month follow-up (T1). Eighteen RRMS patients (11 females, median Expanded Disability Status Scale-EDSS score 1.25, range EDSS score 0–2) were monitored at T0 (mean age 32.33 ± 7.51) and T1 (median EDSS score 1.5, range EDSS score 0–2.5). Patients were grouped into two groups: responders (R, 14 patients) and non-responders (NR, 4 patients) to treatment at T1. Each patient wore an actigraph for one week to record the 24-h motor activity pattern. At T0, NR presented significantly lower motor activity than R between around 9:00 and 13:00. At T1, NR were characterized by significantly lower motor activity than R between around 12:00 and 17:00. Overall, these data suggest that through the 24-h motor activity pattern, we can fairly segregate at T0 patients who will show a therapeutic failure, possibly related to a more active disease, at T1. These patients are characterized by a reduced morning level of motor activation. Further studies on larger populations are needed to confirm these preliminary findings.


2007 ◽  
Vol 13 (2) ◽  
pp. 220-223 ◽  
Author(s):  
A Créange ◽  
I Serre ◽  
M Levasseur ◽  
D Audry ◽  
A Nineb ◽  
...  

We used a global positioning satellite technology odometer to determine the maximum objective walking distance capacity (MOWD) of patients with multiple sclerosis (MS). The MOWD correlated with Expanded Disability Status Scale (EDSS) score (r2 =0.41; P < 0.0001), the MSWS-12 scale (r2 = 0.46; P < 0.0001), time to walk 10 m (r2 = 0.51; P < 0.02) and walking speed (r2 =0.75; P < 0.001). Limitation of walking capacities was measurable up to 4550 m, strikingly above the 500-m limit of the EDSS. This objective odometer is a promising tool for evaluation and follow-up of patients with MS. Multiple Sclerosis 2007; 13: 220–223. http://msj.sagepub.com


2002 ◽  
Vol 8 (2) ◽  
pp. 115-118 ◽  
Author(s):  
A Ghezzi ◽  
C Pozzilli ◽  
M Liguori ◽  
M G Marrosu ◽  
N Milani ◽  
...  

Fifty-four subjects (36 females and 18 males) affected by clinically definite multiple sclerosis (MS) and with onset of the disease at 15 years of age or before were prospectively studied in five Italian MS centres. Female/male ratio was 4.7 in subjects with age ≥12 years, suggesting a role of hormonal changes in triggering MS onset. The mean follow-up duration was 10.9-5.6 years. The functional systems more frequently involved at onset were the pyramidal and brainstem (both in 28% of cases). The onset was monosymptomatic in 31 subjects (57%). The course was relapsing-remitting in 39 subjects (72%) and relapsing-progressive in 15 (28%). Disability was assessed by the Expanded Disability Status Scale (EDSS): the mean score after 8 years of follow up was 3.5 (-2.5). The score was <4 in 68% of cases, between 4 and 6 in 8% of cases, > 6 in 24% of cases. Disability after 8 years was highly predicted by disability in the first year (p=0.008). There was a tendency to a worse prognosis in relation to the number of relapses in the first 2 years (p=0.08). The outcome was not influenced by the characteristics of symptoms at onset, age and gender.


2019 ◽  
Vol 5 (1) ◽  
pp. 205521731882461
Author(s):  
Stanley L Cohan ◽  
Keith Edwards ◽  
Lindsay Lucas ◽  
Tiffany Gervasi-Follmar ◽  
Judy O’Connor ◽  
...  

Background Natalizumab is an effective treatment for relapsing multiple sclerosis. Return of disease activity upon natalizumab discontinuance creates the need for follow-up therapeutic strategies. Objective To assess the efficacy of teriflunomide following natalizumab discontinuance in relapsing multiple sclerosis patients. Methods Clinically stable relapsing multiple sclerosis patients completing 12 or more consecutive months of natalizumab, testing positive for anti-John Cunningham virus antibody, started teriflunomide 14 mg/day, 28 ± 7 days after their final natalizumab infusion. Physical examination, Expanded Disability Status Scale, laboratory assessments, and brain magnetic resonance imaging were performed at screening and multiple follow-up visits. Results Fifty-five patients were enrolled in the study. The proportion of patients relapse-free was 0.94, restricted mean time to first gadolinium-enhancing lesion was 10.9 months and time to 3-month sustained disability worsening was 11.8 months. The mean number of new or enlarging T2 lesions per patient at 12 months was 0.42. Exploratory analyses revealed an annualized relapse rate of 0.08, and a proportion of patients with no evidence of disease activity of 0.68. Forty-seven patients (85.5%) reported adverse events, 95% of which were mild to moderate. Conclusions Teriflunomide therapy initiated without natalizumab washout resulted in a low rate of return of disease activity. Clinicians may consider this a worthwhile strategy when transitioning clinically stable patients off natalizumab to another therapy. ClinicalTrials.gov Identifier: NCT01970410


2004 ◽  
Vol 10 (2) ◽  
pp. 231-242 ◽  
Author(s):  
C Vaney ◽  
S Vaney ◽  
D T Wade

The timed performances of the 10-m timed walk (TMTW) and the nine-ho le peg test (NHPT) of 881 consecutive patients with multiple sclerosis (MS) undergoing a rehabilitation stay, were expressed as a logarithmic function of time in two subscores to form a composite score called the Short and G raphic A bility Score (SaGA S). The subscores (sS) were constructed in such a way that any interval of 0.5 unit corresponds to a change of 25% in the tests. The SaGA S was computed as the mean of four subscores: SaGAS=(2×2-TMTWsS+NHPTsS right hand+NHPTsS left hand). With the aid of a nomogram, the timed values of the tests are easily transformed into the corresponding subscores, which are then displayed graphically to facilitate follow-up over time. The correlation coefficients between the SaGA S and the two motor components of the MS Functional C omposite (MSFC) (r =0.987), the Expanded Disability Status Scale (EDSS)(r = -0.83), the Nottingham EADL Index (r =0.80) and the Rivermead Mobility Index (RMI) (r =0.90) were all statistically significant (P B-0.001), supporting the validity of the measure. SaGA S had a similar sensitivity to the RMI, but was significantly more sensitive than the EDSS in detecting changes occurring during the rehabilitation stay (14.9% versus 5.0%; P B-0.001) and over a one-year follow-up (35.3% versus 19.7%; P B-0.001). C ompared with the motor components of the MSFC, with which it shares several features, SaGA S has several advantages: it does not depend on the stratification of the study population; it does not skew the results of the NHPT towards improvement at the lower end; and it offers an independent assessment of both hands. SaGA S is a simple, intuitive, nonphysician-based measure, which could provide consistent scoring in future clinical trials.


2020 ◽  
Vol 6 (2) ◽  
pp. 205521732092661
Author(s):  
David Jure Hunt ◽  
Anthony Traboulsee

There is a lack of literature documenting the use of alemtuzumab in pediatric multiple sclerosis (MS) patients. Here we describe a 16-year-old and a 17-year-old patient receiving alemtuzumab and being followed for 37 months and 20 months, respectively. Both patients experienced a 1.0 decrease in Expanded Disability Status Scale since initial alemtuzumab infusion and had stable disease. No serious infusion reactions, infections, or definite relapses were recorded on follow-up. Alemtuzumab has been relatively well-tolerated and effective; however, larger, longer-term studies are necessary to understand the specific risks and benefits of alemtuzumab in pediatric MS.


2014 ◽  
Vol 20 (13) ◽  
pp. 1745-1752 ◽  
Author(s):  
Ralph HB Benedict ◽  
Sarah Morrow ◽  
Jonathan Rodgers ◽  
David Hojnacki ◽  
Margaret A Bucello ◽  
...  

Objective: To characterize neuropsychological (NP) test performance during multiple sclerosis (MS) relapse and recovery. Methods: Clinical status was assessed with NP testing and Expanded Disability Status Scale (EDSS) in 24 relapsing patients, and 24 individually-matched, stable controls. All presented with cognitive symptoms as indicated by patient, clinician or caregiver perceived decline, but were free of optic neuritis, ataxia and upper extremity weakness that could compromise NP testing. The presence of enhancing magnetic resonance imaging (MRI) lesions was considered confirmatory of relapse. Relapsing patients were treated with corticosteroids. NP testing and EDSS were compared to pre-relapse baseline levels, and three-month, post-relapse, follow-up. Results: Analyses revealed significant decline on the Symbol Digit Modalities Test (SDMT) ( p=0.005) and worsening on EDSS ( p=0.019). Impairment was observed at the point of relapse in cases but not controls. The groups were no longer different at three-month follow-up. The increment of decline on SDMT was 3.5 raw score points, or roughly 6%. Conclusions: This is the first study to assess NP status changes during MS relapse using well established, reliable metrics. The presence of a clinically meaningful event is substantiated by decline in NP testing, observed or reported cognitive change, and in a subset of patients, gadolinium-enhancing MRI lesions.


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