Dissipation of Motor Sleep Inertia and Motor Wake Inertia in Early Relapsing–Remitting Multiple Sclerosis

While previous studies have described the time course of the dissipation of motor sleep inertia (around 70 min after wake-up time) and motor wake inertia (around 20 min after bedtime) in healthy controls (HCs), the corresponding knowledge for persons with early relapsing–remitting multiple sclerosis (RRMS) is lacking. To fill in this knowledge gap, we carried out a secondary analysis of previously collected data in 35 persons (24 females; mean age = 31.51 ± 7.74 years) with early relapsing–remitting multiple sclerosis (RRMS) and 35 (24 females; mean age = 31.29 ± 8.02) healthy controls (HCs). Each participant wore an actigraphic Micro MotionloggerWatch (Ambulatory Monitoring, Ardlsey, NY, USA) for seven consecutive days. The Functional Linear Modeling statistical framework was adopted to compare the dissipation of motor sleep inertia as well as motor wake inertia between RRMS and HC. As regards motor sleep inertia, no significant differences in motor activity were observed in the first 70 min after the wake-up time; however, with reference to motor wake inertia, the motor activity of RRMS persons was significantly higher than HCs in approximately the first 30 min after bedtime. Despite the small sample size, this pattern of results suggests that the dissipation of motor wake inertia is only slower in persons with RRMS as opposed to HCs

Circadian Activity Rhythm in Early Relapsing-Remitting Multiple Sclerosis

While relapsing-remitting is the most prevalent course of multiple sclerosis, the prognostic/predictive markers of the worsening of symptomatology are still debated. With reference to other diseases, the study of the circadian activity rhythm, according to the theoretical framework of the two-process model of sleep regulation and applying functional linear modeling, proved to be useful to identify a possible marker. The usefulness of the study of circadian activity rhythm in multiple sclerosis is strengthened by recent findings indicating a potential involvement of circadian factors in the multifactorial etiopathology of the disorder. The aim of the present study was to verify whether circadian activity rhythm of early relapsing-remitting multiple sclerosis patients presents specific alterations, through functional linear modeling. Thirty-five relapsing-remitting multiple sclerosis patients (24 females; mean age ± SD = 31.51 ± 7.74) and 35 healthy controls (24 females; mean age ± SD = 31.29 ± 8.02) were enrolled. They wore an actigraph around the non-dominant wrist for one week. Relapsing-remitting multiple sclerosis patients showed a peak in motor activity around 5:00 a.m., higher than that of healthy controls. The timing of the peak in motor activity in the patients could be explained according to the hyperactive hypothalamus-pituitary-adrenal axis and higher cortisol awakening response reported in these patients

External Validation of Three Prognostic Scores for Brain Metastasis Velocity in Patients Treated with Intracranial Stereotactic Radiotherapy

BACKGROUND AND INTRODUCTION Brain metastasis velocity (BMV) has been proposed as a prognostic factor for overall survival (OS) in patients with brain metastases (BMs). In this study, we conducted an external validation and comparative assessment of the performance of all three BMV scores. MATERIALS AND METHODS Patients treated with intracranial stereotactic radiotherapy (SRT) for BM at a single center between 2014 and 2018 were identified. Where possible, all three BMV scores were calculated. Log-rank tests and linear, logistic and Cox regression analysis were used for validation and predictor identification of OS. RESULTS For 333 of 384 brain metastasis patients, at least one BMV score could be calculated. In a sub-group of 187 patients, "classic" BMV was validated as categorical (p<0.0001) and continuous variable (HR 1.02; 95% CI 1.02-1.03; p<0.0001). In a sub-group of 284 patients, "initial" BMV was validated as categorical variable (high-risk vs. low-risk; p<0.01), but not as continuous variable (HR 1.02; 95% CI 0.99-1.04; p=0.224). "Volume-based" BMV could not be validated in a sub-group of 104 patients. On multivariable Cox regression analysis, iBMV (HR 1.85; 95% CI 1.01-3.38; p<0.05) and cBMV (HR 2.32; 95% CI 1.15 4.68; p<0.05) were predictors for OS for intermediate-risk patients after first SRT and first DBFs, respectively. cBMV proved to be the dominant predictor for OS for high-risk patients (HR 2.99; 95% CI 1.30-6.91; p<0.05). CONCLUSION This study externally validated cBMV and iBMV as prognostic scores for OS in patients treated with SRT for BMs whereas validation of vBMV was not achieved

What is the future for agroforestry in Italy?

The successful promotion of agroforestry in Italy depends on both a recognition of tradition and the opportunities for innovation. In Italy, agroforestry has traditionally been a key component of landscape management. Complex systems, based on the integration among crops–livestock–fruit/forest trees, provided a wide variety of products (e.g. food, feed, fibers, fuelwood and timber) and other ecosystem services (e.g. soil erosion control and biodiversity preservation). Silvopastoral systems have been used for centuries and are still managed in marginal areas. The integration of fruits trees (in primis olive trees) with crops and grazing was widely practiced and is still profitable. Coltura promiscua was historically developed integrating fruit and forest trees and particularly multifunctional trees (e.g. Juglans regia L. and Prunus avium L.) to support vines and intercrops. Building on recent research, projects have also focused on innovation in agroforestry. The adoption of shade tolerant forage species and crops has been studied in silvopastoral and olive systems. Silvopastoral systems can significantly offset the greenhouse gas emissions produced by livestock and shield grazing animals from “heat waves”. Integration of fast growing timber trees (like Populus) in arable systems can help reverse the decline in plantation forestry in Italy. Finally, the constraints imposed by the EU agricultural policy, especially the prevalent provisions for monocrops severely limiting the introduction of innovative agroforestry approaches, are discussed. New political measures and certification actions are strongly required

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (&lt;1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score &gt; 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p &lt; 0.001), RR = 2.19 for ICU admission (p &lt; 0.001), and RR = 2.43 for death (p &lt; 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR&nbsp;=&nbsp;2.05, 95%CI&nbsp;=&nbsp;1.39–3.02, p&nbsp;&lt;&nbsp;0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR&nbsp;=&nbsp;0.42, 95%CI&nbsp;=&nbsp;0.18–0.99, p&nbsp;=&nbsp;0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

A Pilot Study of 24-h Motor Activity Patterns in Multiple Sclerosis: Pre-Planned Follow-Up at 2 Years

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 \ub1 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

Circadian Activity Rhythm in Early Relapsing–Remitting Multiple Sclerosis

While relapsing&ndash;remitting is the most prevalent course of multiple sclerosis, the prognostic/predictive markers of the worsening of symptomatology are still debated. With reference to other diseases, the study of the circadian activity rhythm, according to the theoretical framework of the two-process model of sleep regulation and applying functional linear modeling, proved to be useful to identify a possible marker. The usefulness of the study of circadian activity rhythm in multiple sclerosis is strengthened by recent findings indicating a potential involvement of circadian factors in the multifactorial etiopathology of the disorder. The aim of the present study was to verify whether circadian activity rhythm of early relapsing&ndash;remitting multiple sclerosis patients presents specific alterations, through functional linear modeling. Thirty-five relapsing&ndash;remitting multiple sclerosis patients (24 females; mean age &plusmn; SD = 31.51 &plusmn; 7.74) and 35 healthy controls (24 females; mean age &plusmn; SD = 31.29 &plusmn; 8.02) were enrolled. They wore an actigraph around the non-dominant wrist for one week. Relapsing&ndash;remitting multiple sclerosis patients showed a peak in motor activity around 5:00 a.m., higher than that of healthy controls. The timing of the peak in motor activity in the patients could be explained according to the hyperactive hypothalamus-pituitary-adrenal axis and higher cortisol awakening response reported in these patients