The role of the neutrophil-to-lymphocyte ratio (NLR) of peripheral blood has been investigated in relation to several autoimmune diseases. Limited studies have addressed the significance of the NLR ...in terms of being a marker of disease activity in multiple sclerosis (MS).
This is a retrospective study in relapsing-remitting MS patients (RRMS) admitted to the tertiary MS center of Catania, Italy during the period of 1 January to 31 December 2018. The aim of the present study was to investigate the significance of the NLR in reflecting the disease activity in a cohort of early diagnosed RRMS patients.
Among a total sample of 132 patients diagnosed with RRMS, 84 were enrolled in the present study. In the association analysis, a relation between the NLR value and disease activity at onset was found (V-Cramer 0.271,
= 0.013). In the logistic regression model, the variable NLR (
= 0.03 ExpB 3.5, CI 95% 1.089-11.4) was related to disease activity at onset.
An elevated NLR is associated with disease activity at onset in RRMS patients. More large-scale studies with a longer follow-up are needed.
Background: Cladribine tablets are a highly effective option for the treatment of relapsingremitting multiple sclerosis (RRMS).
Objective: The study aims to evaluate the effectiveness of cladribine ...in a real-world setting.
Methods: This prospective real-world study consecutively screened all RRMS patients from seven different MS centers in Sicily (Italy) who completed the 2-year treatment course of cladribine tablets in the period between 11 th March 2019 and 31 st October 2021. Data about Expanded Disability Status Scale (EDSS), relapses, previous treatments, adverse events (AEs) and magnetic resonance imaging (MRI) were collected. Patients who were previously treated with other DMTs were further stratified into moderately active treatment (MAT) and highly active treatment (HAT) patients.
Results: A total of 217 patients (70% women, with a mean age of 38.4 ± 11.3 years) were enrolled. Fifty patients (23.0%) were naïve to treatment and 167 (77%) switched from other disease modifying therapies. After the second year of treatment, about 80% were EDSS progression free, 88% remained relapse-free at T24, and 48% of patients were MRI activity-free. Kaplan Meier analyses showed significant differences between MT and HAT in terms of time to first clinical relapse (HR: 2.43, IC 1.02- 5.76; p = 0.04), time to the first new T1-gadolinium enhancing lesion (HR: 3.43, IC 1.35-8.70; p = 0.009) and time to MRI worsening (HR: 2.42, IC 1.15-5.09; p = 0.02).
Conclusion: This study confirmed that cladribine is an effective treatment for MS, particularly in naïve patients and those who have switched from MATs.
Background: Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic infection caused by John Cunningham virus (JCV) reactivation, potentially associated with natalizumab (NTZ) treatment ...for Multiple Sclerosis (MS). The anti-JCV antibodies titre (JCV index) increases during NTZ treatment; however, the effects of other disease-modifying therapies (DMTs) on the JCV index have not been fully explored. Objective: The aim of the study was to evaluate changes in the JCV index during treatment with several DMTs. Methods: This longitudinal study evaluated the JCV index before starting DMT (T0) and during treatment with DMT (T1). Results: A total of 260 participants (65.4 % females, mean age 43 ± 11.3 ) were enrolled: 68 (26.2 %) treated with fingolimod (FTY), 65 (25 %) rituximab or ocrelizumab (RTX/OCR), 37 (14.2 %) dimethyl-fumarate (DMF), 29 (11.2 %) cladribine (CLD), 23 (8.8 %) teriflunomide (TFM), 20 (7.7 %) interferon or glatiramer acetate (IFN/GA), and 18 (6.9 %) alemtuzumab (ALM). At T1, the percentage of patients with JCV index <0.90 was found to be significantly increased in the ALM group (16.7 % versus 66.7 %, p = 0.05), while the percentage of patients with JCV index >1.51 was found to be significantly reduced in the RTX/OCR group (51.6 % versus 37.5 %, p = 0.04). In the FTY group, a significant reduction in the percentage of patients with JCV index <0.90 was also found (23.5 % versus 1.4 %, p = 0.0006). The mean JCV index was reduced in the RTX/OCR and ALM groups, while a significant increase was observed in the FTY group. Conclusion: DMTs with a T and/or B depleting mechanism of action induced a significant reduction in the JCV index. These results may suggest new possible sequencing strategies potentially maximizing disease control while reducing the PML risk.
Abstract The objective of this current study was to investigate the possible hyperlipidemic and antioxidative effects of Cystoseira crinita sulfated polysaccharide (CCSP) in rats fed with a high-fat ...diet, exhibited an inhibitory activity on pancreatic lipase in vitro. In vivo administration of this extract to HFD-rats lowered body weight and potentially inhibited key enzymes of lipid metabolism and absorption as lipase activity in both plasma and small intestine, which led to a notable decrease of blood LDL- cholesterol (LDL-Ch) and triglycerides (TG) levels, and an increase in HDL-cholesterol (HDL-Ch) levels in HFD-rats. CCSP was also observed to protect the liver-kidney functions efficiently, by decreasing of aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) and Creatine phosphokinase (CPK) activities and creatinine, albumin, T-bilirubin, uric acid, and urea rates in plasma. The histological analysis of liver and kidney tissues further established the positive effect of CCSP.
Abstract
Background
The Coronavirus disease 2019 (COVID-19) caused by the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a pandemic, affecting the therapeutic management ...for Multiple Sclerosis (MS). Any decision regarding the discontinuation of high-potency agents for moderate and highly active MS should be carefully evaluated, taking into account the potential risk of rebound of the disease. In particular, no data about clinical outcome of patients with MS receiving Natalizumab (NTZ) during active COVID-19 infection have been reported yet.
Cases presentation
We reported on 6 patients treated with NTZ for relapsing MS during active COVID-19 infection, who recovered without reporting any worsening or new symptoms. Most of the patients were asymptomatic, with the exception of one patient who had a slight worst COVID-19 clinical course. No patients received O2-therapy or required intensive care. No neurological complications were observed.
Conclusions
This paper reported the clinical outcome of patients with MS receiving NTZ during active COVID-19 infection. This case series suggests that treatment with NTZ during pandemic is relatively safe and might be continued in selected patients who are infected by COVID-19, thereby reducing the risk of MS disease rebound.
Background:
The CLARINET-MS study assessed the long-term effectiveness of cladribine tablets by following patients with multiple sclerosis (MS) in Italy, using data from the Italian MS Registry.
...Methods:
Real-world data (RWD) from Italian MS patients who participated in cladribine tablets randomised clinical trials (RCTs; CLARITY, CLARITY Extension, ONWARD or ORACLE-MS) across 17 MS centres were obtained from the Italian MS Registry. RWD were collected during a set observation period, spanning from the last dose of cladribine tablets during the RCT (defined as baseline) to the last visit date in the registry, treatment switch to other disease-modifying drugs, date of last Expanded Disability Status Scale recording or date of the last relapse (whichever occurred last). Time-to-event analysis was completed using the Kaplan–Meier (KM) method. Median duration and associated 95% confidence intervals (CI) were estimated from the model.
Results:
Time span under observation in the Italian MS Registry was 1–137 (median 80.3) months. In the total Italian patient population (n = 80), the KM estimates for the probability of being relapse-free at 12, 36 and 60 months after the last dose of cladribine tablets were 84.8%, 66.2% and 57.2%, respectively. The corresponding probability of being progression-free at 60 months after the last dose was 63.7%. The KM estimate for the probability of not initiating another disease-modifying treatment at 60 months after the last dose of cladribine tablets was 28.1%, and the median time-to-treatment change was 32.1 (95% CI 15.5–39.5) months.
Conclusion:
CLARINET-MS provides an indirect measure of the long-term effectiveness of cladribine tablets. Over half of MS patients analysed did not relapse or experience disability progression during 60 months of follow-up from the last dose, suggesting that cladribine tablets remain effective in years 3 and 4 after short courses at the beginning of years 1 and 2.
The Multiple Sclerosis Quality of Life-54 (MSQOL-54, 52 items grouped in 12 subscales plus two single items) is the most used MS specific health related quality of life inventory.
To develop a ...shortened version of the MSQOL-54.
MSQOL-54 dimensionality and metric properties were investigated by confirmatory factor analysis (CFA) and Rasch modelling (Partial Credit Model, PCM) on MSQOL-54s completed by 473 MS patients. Their mean age was 41 years, 65% were women, and median Expanded Disability Status Scale (EDSS) score was 2.0 (range 0-9.5). Differential item functioning (DIF) was evaluated for gender, age and EDSS. Dimensionality of the resulting short version was assessed by exploratory factor analysis (EFA) and CFA. Cognitive debriefing of the short instrument (vs. the original) was then performed on 12 MS patients.
CFA of MSQOL-54 subscales showed that the data fitted the overall model well. Two subscales (Role Limitations--Physical, Role Limitations--Emotional) did not fit the PCM, and were removed; two other subscales (Health Perceptions, Social Function) did not fit the model, but were retained as single items. Sexual Satisfaction (single-item subscale) was also removed. The resulting MSQOL-29 consisted of 25 items grouped in 7 subscales, plus 4 single items. PCM fit statistics were within the acceptability range for all MSQOL-29 items except one which had significant DIF by age. EFA and CFA indicated adequate fit to the original two-factor (Physical and Mental Health Composites) hypothesis. Cognitive debriefing confirmed that MSQOL-29 was acceptable and had lost no key items.
The proposed MSQOL-29 is 50% shorter than MSQOL-54, yet preserves key quality of life dimensions. Prospective validation on a large, independent MS patient sample is ongoing.
Background:
Cognitive–motor interference (CMI) is measured by dual-tasking (DT), which involves motor and cognitive tasks. There is no consensus as to whether CMI is present in multiple sclerosis ...(MS).
Objectives:
We investigated the effects of 16 DT conditions by measuring motor complexity, cognitive domain, and task difficulty.
Method:
In total, 40 persons with MS (pwMSs) with Expanded Disease Status Scale (EDSS) 3.2 ± 1.7 and 31 age- and sex-matched healthy controls (HCs) completed 2 single walking, 8 single cognitive, and 2 complex walking tasks and 16 cognitive–motor DT. The main outcomes were mean values of gait velocity and the percentage change from single to DT (motor DT costs, mDTCs) and mean values of cognitive task accuracy and the percentage changes (cognitive DTC, cDTC).
Results:
Two-way analyses of variance showed the main effect of cognitive task yielded an
F
ratio of
F
(4, 268)
= 72.35,
p
< 0.01, for mean gait velocity, and an
F
ratio of
F
(4, 304)
= 17.12,
p
< 0.001, for mDTC, indicating that the mean velocity was significantly lower and the mDTC significantly higher for DS_B (mean = 1.27, SD = 0.03, and mean = 13.52, SD = 1.28, respectively). The main effect of cognitive task yielded an
F
ratio of
F
(4, 116)
= 84.32,
p
< 0.001, with the lowest average accuracy for DS_B (mean = 43.95, SD = 3.33); no effect was found for cDTC. In pwMSs, the EDSS accounted for 28% (
F
= 13.65,
p
= 0.001) of variance in a model predicting the highest mDTC.
Conclusions:
Overall, among different cognitive tasks added, the Digit Span backward was the most interfering cognitive task over gait velocity and accuracy. The effect was similar independently from the motor complexity and the group. PwMSs and HCs behaved in a similar manner at all motor complexity levels and during all cognitive task.
Aims:
We aimed to examine the frequency of polypharmacy in a large cohort of patients at the time of diagnosis of relapsing–remitting multiple sclerosis (RRMS) and to explore its effects on ...discontinuation of first disease-modifying treatment (DMT) using survival analysis.
Methods:
This was a cohort ambispective single-centre study. We enrolled RRMS patients starting their first DMT between 1st January 2013 and 31st December 2015. According to the number of medicines prescribed (except DMTs), we divided the patients into three groups: no-poly RRMS, minor-poly RRMS (from one to three medications), and major-poly RRMS (more than three medications).
Results:
A total of 392 RRMS patients were enrolled (mean age 41.1). The minor-poly RRMS group included 61 patients (15.6%) and the major-poly RRMS group included 112 (28.6%). Individuals in these groups were older and had higher median body mass index (BMI) than patients in the no-poly RRMS group (p < 0.05). Upon multinomial regression analysis, older age at onset was associated with minor and major polypharmacy (OR 1.050, CI 1.010–1.093, p = 0.015 and OR 1.063, CI 1.026–1.101, p = 0.001, respectively) and higher BMI was associated with major polypharmacy (OR 1.186, CI 1.18–1.29, p = 0.001). The rates of discontinuation of first DMT were similar among the three groups (50.7% for no-Poly RRMS, 50.8% for minor-Poly RRMS, and 53.3% for major-Poly RRMS, p = 0.264). At log-Rank test, there were no differences among the three groups (p = 0.834).
Conclusion:
Polypharmacy was more common in older RRMS patients with high BMI.
Epidemiologic studies have raised the possibility that some pesticide compounds induce the neurodegenerative disease amyotrophic lateral sclerosis (ALS), though the available evidence is not entirely ...consistent.
We conducted a population-based case-control study in two Italian populations to assess the extent to which residence in the vicinity of agricultural crops associated with the application of neurotoxic pesticides is a risk factor for ALS, using crop acreage in proximity to the residence as an index of exposure.
Based on 703 cases and 2737 controls, we computed an ALS odds ratio of 0.92 (95% confidence interval 0.78-1.09) for those in proximity to agricultural land. Results were not substantially different when using alternative exposure categories or when analyzing specific crop types, with the exception of a higher risk related to exposure to citrus orchards and olive groves in Southern Italy, though based on few exposed subjects (N = 89 and 8, respectively). There was little evidence of any dose-response relation between crop proximity and ALS risk, and using long-term residence instead of current residence did not substantially change our estimates.
Though our index of exposure is indirect and subject to considerable misclassification, our results offer little support for the hypothesis that neurotoxic pesticide exposure increases ALS risk.
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