Experience with rituximab therapy in a real-life sample of multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune, neuroinflammatory, and neurodegenerative disease of the central nervous system. B cells have recently emerged as a promising target to significantly reduce inflammatory disease activity in MS, with successful trial studies using antiCD20 therapies. However, real-life data about safety and efficacy are limited. OBJECTIVES: To analyze the clinical and radiological inflammatory activity, adherence to therapy, and safety of rituximab (RTX) in an MS patients' sample, treated from 2015 to 2018 in our center PATIENTS AND METHODS: Retrospective study on prospectively collected data about relapses, disability progression, and radiological activity (new T2 lesions and Gd-enhancing lesions) were recorded and used to assess no evidence of disease activity (NEDA) at 12 months. RTX-related adverse events were recorded. RTX was administered intravenously at a dosage of 1000 mg twice 2 weeks apart, then every 6 months. RESULTS: Sixty-nine patients were included. Fifty-three (76.8%) had a relapsing-remitting, two a primary progressive course, and 14 a secondary progressive course. The mean follow-up period was 16 ± 9.7 months. Thirty-five (50.7%) patients had relapses in the year prior to RTX therapy, with a mean annualized relapse rate of 0.75, significantly reduced to 0.36 at 12 months (p < 0.001). Among the 36 patients included in the study who had an MRI available at 12 months, MRI activity was reduced from 88% (n = 32) to 8.3% (n = 3) at follow-up (p < 0.001). Twelve (17.4%) patients suspended RTX during the study. CONCLUSIONS: Our real-life experience confirms that off-label therapy with RTX may represent a valid, cost-effective therapeutic option in MS.

Cognitive impairment in multiple sclerosis: An exploratory analysis of environmental and lifestyle risk factors.

BACKGROUND: Many potentially modifiable risk factors for MS are investigated. It is not known, however, if these factors also apply to MS-related cognitive impairment (CI), a frequent consequence of MS. OBJECTIVE: The aim of our study was to assess risk factors for CI in MS patients, focusing on environmental exposures, lifestyle and comorbidities. METHODS: We included MS patients referring to MS Centers in Florence and Barletta between 2014 and 2017. Neuropsychological performance was assessed through the Rao's battery and Stroop test, cognitive reserve (premorbid intelligence quotient-IQ) was evaluated using the National Adult Reading Test (NART). Potential risk factors were investigated through a semi-structured questionnaire. RESULTS: 150 patients were included. CI was detected in 45 (30%) subjects and was associated with older age (p<0.005), older age at MS onset (p = 0.016), higher EDSS score (p<0.005), progressive disease course (p = 0.048) and lower premorbid IQ score (p<0.005). As for risk factors, CI was related with lower physical activity in childhood-adolescence (p<0.005). In women, hormonal therapy resulted to be protective against CI (p = 0.041). However, in the multivariable analysis, the only significant predictors of CI were older age (p<0.05; OR 1.06, 95% CI 1.02-1.10) and lower premorbid IQ (p<0.05; OR 0.93, 95% CI: 0.88-0.98). Removing IQ from the model, CI was associated with higher EDSS (p = 0.030; OR 1.25, 95% CI 1.02-1.53) and, marginally, previous physical activity (p = 0.066; OR 0.49, 95% CI: 0.23-1.05). CONCLUSIONS: Our findings suggest that physical activity in childhood-adolescence could be a contributor to cognitive reserve building, thus representing a potential protective factors for MS-related CI susceptible to preventive strategies.

Paternal therapy with disease modifying drugs in multiple sclerosis and pregnancy outcomes: a prospective observational multicentric study.

BACKGROUND: Most of Multiple Sclerosis (MS) patients undergo disease modifying drug (DMD) therapy at childbearing age. The objective of this prospective, collaborative study, was to assess outcomes of pregnancies fathered by MS patients undergoing DMD. METHODS: Structured interviews on pregnancies fathered by MS patients gathered in the Italian Pregnancy Dataset were collected; pregnancies were divided according to father exposure or unexposure to DMD at time of procreation. Treatment were compared with multivariable logistic and linear models. RESULTS: Seventy-eight pregnancies fathered by MS patients were tracked. Forty-five patients were taking DMD at time of conception (39 beta-interferons, 6 glatiramer acetate), while 33 pregnancies were unexposed to DMD. Seventy-five pregnancies ended in live-births, 44 in the exposed and 31 in the unexposed group. No significant differences between the two groups were found in the risk of spontaneous abortion or malformations (p > 0.454), mean gestational age (p = 0.513), frequency of cesarean delivery (p = 0.644), birth weight (p = 0.821) and birth length (p = 0.649). In comparison with data of the Italian general population, the proportion of spontaneous abortion and caesarean delivery in exposed pregnancies fell within the estimates, while the proportion of pre-term delivery in the exposed group was higher than expected. CONCLUSIONS: Our data indicate no association between paternal DMD exposure at time of conception and risk of spontaneous abortion, adverse fetal outcomes and congenital malformations. Further studies clarifying the role of DMD fathers intake prior and during pregnancy are desirable, to supply guidelines for clinical practice.

Ventilatory strategies in the six-minute walk test in older patients receiving a three-week rehabilitation programme after cardiac surgery through median sternotomy.

BACKGROUND: Although the six-minute walk test (6MWT) is widely used in cardiac rehabilitation, little is known about the ventilatory strategies adopted by older patients who have recently undergone median sternotomy, in order to meet the increased metabolic demand in the 6MWT. METHODS: Using a portable gas-analyser we assessed the breathing patterns in the 6MWT before and after a 3-week rehabilitation programme in 84 older patients, 58 men and 26 women, mean age 71 years (standard deviation (SD) 6 years), who had undergone median sternotomy. RESULTS: After rehabilitation, patients increased end-test ventilation (33.1 l (SD 9.8) vs. 30.9 l (SD 8.4), p < 0.001) by increasing tidal volume (1.158 l (SD 0.298) vs. 1.065 l (SD 0.255), p < 0.001), while breathing frequency remained unchanged (29.9 bpm (SD 5.4) vs. 30.2 bpm (SD 5.8), p = 0.621). As a consequence, the ventilatory equivalent for CO2, was significantly improved (39.9 (SD 5.3) vs. 43.5 (SD 7.4), p < 0.001). Furthermore, the improvement in ventilatory efficiency was significantly (p < 0.001) correlated with the improvement in the distance walked on the 6MWT. CONCLUSION: Older patients who have undergone median sternotomy meet the increased metabolic demand on the 6MWT after cardiac rehabilitation by increasing tidal volume. Accordingly, we should consider including as a routine specific exercises for inspiratory muscle training in current rehabilitation programmes to reduce inspiratory muscle effort and further improve ventilatory efficiency.

Pregnancy and fetal outcomes after Glatiramer Acetate exposure in patients with multiple sclerosis: a prospective observational multicentric study.

BACKGROUND: Only few studies have assessed safety of in utero exposure to glatiramer acetate (GA). Following a previous study assessing the safety of interferon beta (IFNB) pregnancy exposure in multiple sclerosis (MS), we aimed to assess pregnancy and fetal outcomes after in utero exposure to GA, using the same dataset, with a specific focus on the risk of spontaneous abortion. MATERIALS AND METHODS: We recruited MS patients, prospectively followed-up in 21 Italian MS Centres, for whom a pregnancy was recorded in the period 2002-2008. Patients were divided into 2 groups: drug-exposed pregnancies (EP: suspension of the drug less than 4 weeks from conception); non-exposed pregnancies (NEP: suspension of the drug at least 4 weeks from conception or never treated pregnancies). All the patients were administered a structured interview which gathered detailed information on pregnancy course and outcomes, as well as on possible confounders. Multivariate logistic and linear models were used for treatment comparisons. RESULTS: Data on 423 pregnancies were collected, 17 were classified as EP to GA, 88 as EP to IFNB, 318 as NEP. Pregnancies resulted in 16 live births in the GA EP, 75 live births in the IFNB EP, 295 live births in the NEP. GA exposure was not significantly associated with an increased risk of spontaneous abortion (OR = 0.44;95% CI 0.044-4.51;p = 0.49). Mean birth weight and length were not significantly different in pregnancies exposed to GA than in non exposed pregnancies (p = 0.751). The frequency of preterm delivery, observed in 4 subjects exposed to GA (25% of full term deliveries), was not significantly higher in pregnancies exposed to GA than in those non exposed (p > 0.735). These findings were confirmed in the multivariate analysis. There were neither major complications nor malformations after GA exposure. CONCLUSIONS: Data in our cohort show that mother's GA exposure is not associated with a higher frequency of spontaneous abortion, neither other negative pregnancy and fetal outcomes. Our findings point to the safety of in utero GA exposure and can support neurologists in the therapeutic counselling of MS women planning a pregnancy.

Cognitive rehabilitation in children and adolescents with multiple sclerosis.

Cognitive impairment can be detected in a sizeable proportion of pediatric multiple sclerosis (MS) patients. It involves memory, complex attention, information processing speed, executive functions, linguistic abilities, and intelligent quotient. It has a great impact on school, everyday and social activities, and significantly progresses overtime in the great majority of the subjects. These findings highlight the importance of a comprehensive and systematic assessment of MS-related cognitive difficulties in pediatric cases. Moreover, despite the acknowledged relevance of cognitive impairment in this age range, specific interventions for pediatric MS are lacking. As for rehabilitative strategies, there is some evidence of efficacy in other diseases, in particular brain trauma, tumor, and stroke. The development of effective rehabilitative strategies tailored to the needs of young MS patients is a priority for future research in the field.