Limited longitudinal studies have been conducted on gait impairment progression overtime in non-disabled people with multiple sclerosis (PwMS). Therefore, a deeper understanding of gait changes with ...the progression of the disease is essential. The objective of the present study was to describe changes in gait quality in PwMS with a disease duration ≤ 5 years, and to verify whether a change in gait quality is associated with a change in disability and perception of gait deterioration. We conducted a multicenter prospective cohort study. Fifty-six subjects were assessed at baseline (age: 38.2 ± 10.7 years, Expanded Disability Status Scale (EDSS): 1.5 ± 0.7 points) and after 2 years, participants performed the six-minute walk test (6MWT) wearing inertial sensors. Quality of gait (regularity, symmetry, and instability), disability (EDSS), and walking perception (multiple sclerosis walking scale-12, MSWS-12) were collected. We found no differences on EDSS, 6MWT, and MSWS-12 between baseline and follow-up. A statistically significant correlation between increased EDSS scores and increased gait instability was found in the antero-posterior (AP) direction (r = 0.34, p = 0.01). Seventeen subjects (30%) deteriorated (increase of at least 0.5 point at EDSS) over 2 years. A multivariate analysis on deteriorated PwMS showed that changes in gait instability medio-lateral (ML) and stride regularity, and changes in ML gait symmetry were significantly associated with changes in EDSS (F = 7.80 (3,13), p = 0.003, R2 = 0.56). Moreover, gait changes were associated with a decrease in PwMS perception on stability (p < 0.05). Instrumented assessment can detect subtle changes in gait stability, regularity, and symmetry not revealed during EDSS neurological assessment. Moreover, instrumented changes in gait quality impact on subjects’ perception of gait during activities of daily living.
Capacitive and resistive electric transfer (CRET) therapy is a physical treatment modality commonly used to treat musculoskeletal pain. It normally uses a longwave radiofrequency of ~0.5 MHz. The ...system consists of a neutral plate and two different electrodes that can transfer energy in two modalities: capacitive and resistive. The aim of this systematic review was to identify and summarize the available data in the literature on this physical modality. From a search of articles published before December 2019 in MEDLINE and Scopus indexed journals, we retrieved 276 articles, 13 of which met the inclusion criteria for this review. Most articles dealt with musculoskeletal disorders, mainly spine disorders and knee osteoarthritis. More than 75% of the studies used a similar range of frequency (440-600 KHz). Almost all described an improvement in strength and function and reduced pain intensity after the treatment. Although nine of the 13 studies (70%) were randomized controlled trials, only two had a low risk of bias according to the Cochrane library assessment tool. CRET seems to be an effective therapy to decrease pain, and improve the quality of life and disability of patients affected by musculoskeletal disorders. There is no study on symptoms of patients with neurological disorders. Further research is necessary to standardize the therapeutic protocols across different orthopedic diseases, and to assess the benefits of CRET in other fields such as neurological or rheumatologic disorders.
Background:
The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested.
Objective:
The aim of this study was to determine the ...demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis.
Methods:
Patients with adult-onset relapsing–remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed.
Results:
A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02, p < 0.001), longer disease duration (HR = 1.01, p = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30, p < 0.001), more rapid disability trajectory (HR = 2.82, p < 0.001) and greater number of relapses in the previous year (HR = 1.07, p = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62, p = 0.039) and disease-modifying therapy exposure (HR = 0.71, p = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion.
Conclusion:
Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression.
Background:
Little is known about COVID-19 course and outcomes after a third booster dose of mRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treated with ...ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response to mRNA-vax.
Objectives:
The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCR and FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab (NTZ).
Methods:
Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNA-Vax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use.
Results:
Overall, 290 pwMS (79 NTZ, 126 OCR, and 85 FNG) from 17 Italian MS centers were included. Age, Expanded Disability Status Scale (EDSS) score, MS phenotype, disease, and treatment duration were significantly different across groups. PwMS who had COVID-19 on OCR and FNG compared with those on NTZ were slightly more symptomatic with higher hospitalization rates (11.1% vs 7.1% vs 1.3%, respectively). Regression models showed that the majority of the differences observed were not related to the disease-modifying treatments (DMTs) used. No fatal cases were observed.
Conclusion:
Our results support the effectiveness of the third booster dose of mRNA-Vax against severe forms of COVID-19 in pwMS treated with OCR and FNG.
Objective:
This propensity score–matched analysis from MSBase compared the effectiveness of cladribine with interferon β, fingolimod or natalizumab.
Methods:
We identified all patients with ...relapse-onset multiple sclerosis, exposure to the study therapies and ⩾1-year on-treatment follow-up from MSBase. Three pairwise propensity score–matched analyses compared treatment outcomes over 1 year. The outcomes were hazards of first relapse, disability accumulation and disability improvement events. Sensitivity analyses were completed.
Results:
The cohorts consisted of 37 (cladribine), 1940 (interferon), 1892 (fingolimod) and 1410 patients (natalizumab). The probability of experiencing a relapse on cladribine was lower than on interferon (p = 0.05), similar to fingolimod (p = 0.31) and higher than on natalizumab (p = 0.042). The probability of disability accumulation on cladribine was similar to interferon (p = 0.37) and fingolimod (p = 0.089) but greater than natalizumab (p = 0.021). The probability of disability improvement was higher on cladribine than interferon (p = 0.00017), fingolimod (p = 0.0025) or natalizumab (p = 0.00099). Sensitivity analyses largely confirmed the above results.
Conclusion:
Cladribine is an effective therapy for relapse-onset multiple sclerosis. Its effect on relapses is comparable to fingolimod and its effect on disability accrual is comparable to interferon β and fingolimod. Cladribine may potentially associate with superior recovery from disability relative to interferon, fingolimod and natalizumab.
Objectives:
To assess the impact of timing of natalizumab cessation/redosing on long-term maternal and infant outcomes in 72 out of the original 74 pregnancies of the Italian Pregnancy Dataset in ...multiple sclerosis (MS).
Methods:
Maternal outcomes in patients who received natalizumab until conception and restarted the drug within 1 month after delivery (“treatment approach,” (TA)) and patients who stopped natalizumab before conception and/or restarted the drug later than 1 month after delivery (“conservative approach,” (CA)) were compared through multivariable Cox regression analyses. Pediatric outcomes were assessed through a semi-structured questionnaire.
Results:
After a mean follow-up of 6.1 years, CA (hazard ratio (HR) = 4.1, 95% CI 1.6–10.6, p = 0.003) was the only predictor of relapse occurrence. Worsening on the Expanded Disability Status Scale (EDSS) was associated with higher annualized relapse-rate during the follow-up (HR = 3.3, 95% CI 1.4–7.9 p = 0.007). We found no major development abnormalities in children.
Discussion:
Our data confirm that TA reduces the risk of disease activity; we did not observe an increase in major development abnormalities in the child.
The New Anatomy of Neuroimmunology Solaro, Claudio; Barratt, David; Vaccarezza, Mauro
Immuno,
03/2022, Letnik:
2, Številka:
1
Journal Article
Recenzirano
Odprti dostop
In the past few years, a renowned interest in the interplay between the immune system and central nervous systems (CNS) has sparked a wealth of new experimental studies. Two recent publications in ...Science shed new light on the “resident” immune cell populations in the CNS and their functions in homeostasis and pathological status, with potential implications in understanding CNS disease mechanisms and in designing new “intelligent” therapies.
Background
Natalizumab (NTZ) is an effective treatment for relapsing–remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy due to safety or ...efficacy issues. The aim of our study was to evaluate the NTZ discontinuation rate and reasons of discontinuation in a large Italian population of RRMS patients.
Materials and methods
The data were extracted from the Italian MS registry in May 2018 and were collected from 51,845 patients in 69 Italian multiple sclerosis centers. MS patients with at least one NTZ infusion in the period between June 1st 2012 to May 15th 2018 were included. Discontinuation rates at each time point were calculated. Reasons for NTZ discontinuation were classified as “lack of efficacy”, “progressive multifocal leukoencephalopathy (PML) risk” or “other”.
Results
Out of 51,845, 5151 patients, 3019 (58.6%) females, with a mean age of 43.6 ± 10.1 years (median 40), were analyzed. Out of 2037 (39.5%) who discontinued NTZ, a significantly higher percentage suspended NTZ because of PML risk compared to lack of efficacy 1682 (32.7% of 5151) vs 221 (4.3%),
p
< 0.001; other reasons were identified for 99 (1.9%) patients. Patients discontinuing treatment were older, had longer disease duration and worse EDSS at the time of NTZ initiation and at last follow-up on NTZ treatment. The JCV index and EDSS at baseline were predictors for stopping therapy (HR 2.94, 95% CI 1.22–4.75;
p
= 0.02; HR 1.36, 95% CI 1.18–5.41;
p
= 0.04).
Conclusions
Roughly 60% of MS patients stayed on NTZ treatment during the observation period. For those patients in whom NTZ discontinuation was required, it was mainly due to PML concerns.
Background:
The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear.
Objective:
To determine whether early non-disabling relapses ...predict disability accumulation in RRMS.
Methods:
We redefined mild relapses in MSBase as ‘non-disabling’, and moderate or severe relapses as ‘disabling’. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up.
Results:
People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00–1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15–1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71–1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically.
Conclusion:
This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.
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