Background: Although physical rehabilitation is commonly administered to MS patients, its efficacy has not been established. Objective: We assessed the efficacy of an inpatient physical rehabilitation program on impairment, disability, and quality of life of MS patients with a randomized, single-blind, controlled trial. Methods: Fifty ambulatory MS patients were assigned to 3 weeks of inpatient physical rehabilitation (study treatment) or exercises performed at home (control treatment). Patients were evaluated at baseline and at 3, 9, and 15 weeks by a blinded examining physician. Results: No changes in impairment occurred in either group, as measured by the Expanded Disability Status Scale. At the end of the intervention the study group improved significantly in disability, as assessed by the Functional Independence Measure (FIM) motor domain, compared with controls (p = 0.004), and the improvement persisted at 9 weeks (p = 0.001). The effect size statistic was usually large or moderate in all scale scores of the FIM motor domain at 3 weeks and moderate to fair thereafter. The study group also improved in overall health-related quality of life profile compared with controls; however, the difference was significant only for the mental composite score at 3 (p = 0.008) and 9 weeks (p = 0.001). Conclusions: Despite unchanging impairment, physical rehabilitation resulted in an improvement in disability and had a positive impact on mental components of health-related quality of life perception at 3 and 9 weeks.

OBJECTIVES Health related quality of life (HRQOL) inventories are multi-dimensional measures of patient-centred health status developed for clinical research. The MS quality of life 54 (MSQOL-54) is an MS-specific HRQOL inventory originally devised for English speaking patients. It consists of a core measure, the 36-item short form health survey (SF-36) previously adapted into Italian, and 18 additional items exploring domains relevant to patients with MS (MS-18 module). The authors translated and culturally adapted into Italian the MS-18 module of the MSQOL-54 questionnaire, and clinically validated the whole questionnaire. METHODS The MS-18 module was translated following the methodology of the International Quality of Life Assessment (IQOLA) project. The MSQOL-54 was validated in 204 consecutive patients with MS seen between April and September 1997 at three participating centres. The questionnaire was explained by the physician who also administered the expanded disability status scale (EDSS) and mini mental status scale examination, and the patient filled in the MSQOL-54 and Beck depression inventory questionnaires (BDI), with assistance if required. The contribution of impairments and disabilities to MSQOL-54 scores were assessed, and mean scores were compared with normative data for the general Italian population, and with the original sample of United States MS patients. RESULTS The mean age of the 204 patients was 42 years; mean EDSS score was 4.5 (range 0-8.5). Patients’ participation in the assessment was satisfactory, and all scales satisfied the usual psychometric standards. The characteristics of the United States sample matched those of our patients in all but gender (72% United States patientsv 52% Italian patients were women), and education (90% United States patients and 44% Italian patients completed high school); MSQOL-54 profiles were also similar. The EDSS was significantly associated with the physical health composite but not with the mental health composite score. Multiple linear regression modelling showed that age and BDI independently predicted physical health composite (p < 0.001), and mental health composite (p < 0.001). Clinical worsening in the previous year had an independent effect on the physical health composite (p < 0.001). CONCLUSIONS The Italian version of MSQOL-54 is easy to administer and is well accepted by patients. Neurological impairment has a limited influence on perceived quality of life, while age and depressive symptoms has a major influence.

Objective: To evaluate Bacille Calmette-Guérin (BCG) effects after clinically isolated syndromes (CIS). Methods: In a double-blind, placebo-controlled trial, participants were randomly assigned to receive BCG or placebo and monitored monthly with brain MRI (6 scans). Both groups then entered a preplanned phase with IM interferon-β-1a for 12 months. From month 18 onward, the patients took the disease-modifying therapies (DMTs) that their neurologist considered indicated in an open-label extension phase lasting up to 60 months. Results: Of 82 randomized subjects, 73 completed the study (33 vaccinated and 40 placebo). During the initial 6 months, the number of cumulative lesions was significantly lower in vaccinated people. The relative risks were 0.541 (95% confidence interval [CI] 0.308–0.956; p = 0.03) for gadolinium-enhancing lesions (the primary endpoint), 0.364 (95% CI 0.207–0.639; p = 0.001) for new and enlarging T2-hyperintense lesions, and 0.149 (95% CI 0.046–0.416; p = 0.001) for new T1-hypointense lesions. The number of total T1-hypointense lesions was lower in the BCG group at months 6, 12, and 18: mean changes from baseline were −0.09 ± 0.72 vs 0.75 ± 1.81 (p = 0.01), 0.0 ± 0.83 vs 0.88 ± 2.21 (p = 0.08), and −0.21 ± 1.03 vs 1.00 ± 2.49 (p = 0.02). After 60 months, the cumulative probability of clinically definite multiple sclerosis was lower in the BCG + DMT arm (hazard ratio = 0.52, 95% CI 0.27–0.99; p < 0.05), and more vaccinated people remained DMT-free (odds ratio = 0.20, 95% CI 0.04–0.93; p = 0.04). Conclusions: Early BCG may benefit CIS and affect its long-term course. Classification of evidence: BCG, as compared to placebo, was associated with significantly reduced development of gadolinium-enhancing lesions in people with CIS for a 6-month period before starting immunomodulating therapy (Class I evidence).

Pathogenesis of autoimmune disorders, including Multiple Sclerosis (MS), has been linked to an alteration of the resident microbial commensal community and of the interplay between the microbiota and the immune system. Dietary components such as fibers, acting on microbiota composition, could, in principle, result in immune modulation and, thus, could be used to obtain beneficial outcomes for patients. We verified this hypothesis in a pilot study involving two groups of clinically similar Relapsing-Remitting (RR) MS patients who had undergone either a high-vegetable/low-protein diet (HV/LP diet group; N=10) or a standard western diet (WD group; N=10) for at least 12 months. Gut microbiota composition, analyzed by 16S V4 rRNA gene sequencing and immunological profiles, were examined after a minimum of 12 months of diet. Results showed that, in the HV/LP diet group compared to the WD group: 1) Lachnospiraceae family was significantly more abundant; 2) IL-17-producing T CD4+ lymphocytes (p= 0.04) and PD-1 expressing T CD4+ lymphocytes (p= 0.0004) were significantly decreased; and 3) PD-L1 expressing monocytes (p= 0.009) were significantly increased. In the HV/LP diet group, positive correlations between Lachnospiraceae and both CD14+/IL-10+ and CD14+/TGFbeta+ monocytes (RSp=0.707, p=0.05 and RSp= 0.73, p=0.04; respectively), as well as between Lachnospiraceae and CD4+/CD25+/FoxP3 T lymphocytes (RSp= 0.68,p=0.02) were observed. Evaluation of clinical parameters showed that in the HV/LP diet group alone the relapse rate during the 12 months follow up period and the EDSS score at the end of the study period were significantly reduced.. Diet modulates dysbiosis and improves clinical parameters in MS patients by increasing anti-inflammatory circuits. Because Lachnospiraceae favour Treg differentiation as well as TGFbeta and IL-10 production this effect could be associated with an increase of these bacteria in the microbiota.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system and a major cause of disability in young adults. Recently, there has been a growing interest in the development of innovative ways to deliver rehabilitation care outside of a hospital setting. The aim was to conduct a systematic review and a meta-analysis of the efficacy of an integrated telerehabilitation approach (ITA) on motor, cognitive and participation outcomes delivered to people with MS (pwMS). We systematically searched for original manuscripts regarding ITA in pwMS. Efficacy on motor, cognitive and participation outcomes was measured as the standardized mean difference (Hedges' g) of pre and post training. Nine studies encompassing 716 pwMS diagnosis were included. The overall effect of ITA was: large for motor outcomes (g = 1.05; p = 0.013); small for cognitive performance outcomes (g = 0.16; p = 0.237); and small for participation outcomes (g = 0.15; p = 0.259). Domain-specific results showed that the effect on motor disability was large (g = 1.18), while on gait and balance was medium (g = 0.32 and g = 0.48, respectively). Moreover, all effects on single cognitive domains were small. Finally, among the single participation outcomes considered (depression, fatigue, daily functioning, quality of life and self-efficacy) only depression showed a nearly medium effect (g = 0.30). PwMS can benefit from ITA in the treatment of motor symptoms according to the current model of continuity of care. However, the low efficacy of ITA on cognition and participation domains suggests the necessity to develop intervention models that include a broader spectrum of needs and objectives.