Pregnancy planning and outcomes in patients with multiple sclerosis after mitoxantrone therapy: a monocentre assessment.

BACKGROUND AND PURPOSE: Patients with multiple sclerosis (MS) have many pregnancy-related doubts and fears. Careful counselling is thus important. Mitoxantrone (MITO) is used in patients with aggressive MS and may affect reproductive capacity. The aim of this study was to investigate pregnancy planning and outcomes in patients with MS treated with MITO, both before and after the treatment. METHODS: Patients with MS previously treated with MITO were recruited. Clinical, demographic and treatment data were recorded. A questionnaire regarding the planning and outcomes of all pregnancies was administered. Parametric and non-parametric tests were performed using SPSS 22 software. RESULTS: A total of 238 patients (female/male, 158/80) were included; 106 subjects planned a pregnancy before MITO and 40 after MITO. Of these, respectively, 102 (97%) and 35 (85%) resulted in conception, 19 (19%) and 7 (18%) in miscarriage, 6 (6%) and 1 (3%) in abortion and 98 (96%) and 32 (91%) were full-term pregnancies. A total of 96 patients (40%) planned a pregnancy only before MITO (and not after), whereas 30 (13%) planned a pregnancy only after MITO (and not before) (P < 0.01). A total of 103 patients did not plan a pregnancy before MITO and 198 did not plan a pregnancy after MITO. The reasons included lack of interest or a partner, fear of MS and infertility. All of the babies born were healthy until the end of follow-up. CONCLUSIONS: Mitoxantrone does not affect the ability to conceive or pregnancy outcomes. We found no differences in pregnancies, abortions or miscarriages before and after MITO. The tendency to plan pregnancies decreased significantly after MITO. Our findings may be useful for improving the quality of life of patients and the approach taken by neurologists.

Clinical activity after fingolimod cessation: disease reactivation or rebound?

BACKGROUND AND PURPOSE: There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself or whether it is due to the natural course of highly active multiple sclerosis (MS). Our aim was to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS. METHODS: Patients with relapsing-remitting MS who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis. RESULTS: A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Amongst these patients, five (5%) had a reactivation that was considered to be a rebound. CONCLUSIONS: The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described.

Performance in daily activities, cognitive impairment and perception in multiple sclerosis patients and their caregivers.

BACKGROUND: The relationship between cognitive assessment results in multiple sclerosis (MS) and performance in daily activities (DAs) remains unclear. Our study aimed to evaluate the relationship between cognitive functions (CF) measured by tests, performance in DAs, and the perception of CF in patients and their caregivers (CG) in MS. METHODS: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was used to evaluate cognitive status. We created an ad hoc questionnaire (DaQ) to assess performance in DAs not requiring specific motor skills. We used the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) to measure each patient self-judgment and caregiver's perception of CF. RESULTS: Forty-nine patients and their caregivers were included in the study. Significant correlations were found between the BICAMS and the DaQ (Symbol Digit Modalities Test (SDMT): r = - 0.48, p < 0.001; California Verbal Learning Test (CVLT): r = - 0.33, p = 0.01; Brief Visual Memory Test (BVMT-R): r = - 0.42; p = 0.002); patients self-judgment (SDMT: r = - 0.38, p = 0.004; CVLT: r = - 0.26, p = 0.03); caregiver perception of patient's CF (SDMT: r = - 0.52, p < 0.001; CVLT: r = - 0.3, p = 0.01; BVMT-R: r = - 0.42, p = 0.002). The difference in perception between the patients and their caregivers was related to patient age (p = 0.001) and severity of cognitive impairment (p = 0.03). CONCLUSIONS: Cognitive assessment results show a significant correlation with performance in daily activities and with patients and, especially, caregiver perception of cognitive impairment. These data support the importance of a routine evaluation of cognitive function in MS that includes an anamnestic evaluation of patients, and, when possible, consideration of the caregiver's point of view.

Combining HLA-DRB1-DQB1 and Mycobacterium Avium Subspecies Paratubercolosis (MAP) antibodies in Sardinian multiple sclerosis patients: associated or independent risk factors?

BACKGROUND: Amongst Sardinians the human leukocyte antigen (HLA) DRB1-DQB1 haplotypes *15:02-*06:01, *16:01-*05:02, *14:01-4-*05:03 are protective for multiple sclerosis (MS), while *13:03-*03:01, *04:05-*03:01, *03:01-*02:01, *15:01-*06:02 and Mycobacterium avium subspecies paratubercolosis (MAP) are predisposing factors. We studied the correlation between MAP and HLA. METHODS: Five hundred thirty-one patients were searched for anti-MAP2694 antibodies, DRB1-DQB1 genotyping was performed. The haplotypes were classified as predisposing, neutral or protective. RESULTS: Anti-MAP2694 were found in 23 % of subjects carrying one protective HLA versus 32 % without (p = 0.04). CONCLUSIONS: We showed a lower frequency of Abs in patients with protective HLA. These haplotypes could have a protective role for both MS and MAP.

Attitude towards physical activity in patients with multiple sclerosis: a cohort study.

Multiple sclerosis (MS) is a long-lasting neurological disease with onset in young adult age. Patients with MS are less active than healthy people, and their sedentary lifestyle might lead to secondary diseases or worsening of symptoms, disability and quality of life. In the study, we evaluated the attitude of physical activity (PA) of a group of MS patients and the differences in practice PA before and after the diagnosis. A randomly recruited group of patients with MS fulfilled a questionnaire about their attitudes towards PA before the onset and after the diagnosis of the disease. Clinical and demographic data were recorded. Out of 118 patients, 37 % practiced PA only before the diagnosis, 9 % only after and 52 % during both periods. After the diagnosis, 64 % of participants noted some negative differences in PA, in particular less physical resistance and worsening of symptoms, and 38 % stopped PA. However, patients referred benefits from PA after diagnosis. Individual exercises rather than group activities were preferred after diagnosis. Only 26 % of patients knew that adapted PA existed and the differences between adapted PA and classic physiotherapy. We observed a reduction in the practice of PA in patients after the diagnosis of MS, in particular for disease-related reasons. Nevertheless, active patients referred benefits from PA. It is important to know the point of view of patients towards developing individualized training programs. In this way, it could be possible to achieve more benefits from PA and reduce the negative effects.

Progressive multiple sclerosis and mood disorders.

Mood disorders are very common among multiple sclerosis (MS) patients, but their frequency in patients with progressive course (PMS) has not been adequately researched. Our study aimed to determine the frequency of mood disorders among patients with PMS compared with those with relapsing-remitting MS (RMS) and to explore the associations with disability and disease duration. The study included consecutive outpatients affected by MS according the 2010 revised Mc Donald diagnostic criteria. Psychiatric diagnoses were determined according to DSM-IV by psychiatrists using structured interview tools (ANTAS-SCID). Demographic and clinical data of patients were also collected. Disease courses were defined according to the re-examined phenotype descriptions by the Committee and MS Phenotype Group. Intergroup comparisons were performed by Chi-square test, while logistic regression analysis was performed to assess possible factors associated with mood disorders. In total, 240 MS patients (167 women) were enrolled; of these, 18 % (45/240) had PMS. The lifetime DSM-IV major depression diagnosis (MDD) was established in 40 and 23 % of the PMS and RMS patients, respectively. Using logistic regression analysis, the presence of MDD was independent from disease duration and disability and dependent on PMS course (P = 0.02; OR 2.2). Patients with PMS presented with MDD more frequently than those with RMS, independently from disease duration and physical disability. These findings highlight the importance of considering mood disorders, especially MDD, in the management of PMS patients.

A genetic study of the FMR1 gene in a Sardinian multiple sclerosis population.

Multiple sclerosis (MS) is a complex autoimmune disease originated from the interplay between genetic and environmental factors. An overlap of clinical and neuroradiological parameters has been described between MS and an adult-onset neurodegenerative disorder, the fragile-X-associated tremor/ataxia syndrome (FXTAS). This syndrome is caused by a trinucleotide premutation expansion of a CGG sequence in the 55-200 repeat range, which is located in the fragile-X mental retardation 1 (FMR1) gene. Female premutation carriers have an increased propensity for immune-mediated disorders. Recently, a case of co-occurrence of MS and FXTAS was reported. Assuming that the premutation expansion may play a role in the MS susceptibility, we evaluated its frequency in a cohort of MS patients from Sardinia, an island characterized by a very high frequency of MS. Nuclear DNA was extracted by standard methods, purified with bisulfite treatment and then amplified twice by PCR with specific primers. Microsatellite analysis was performed and emizogotic subjects were sequenced. Clinical data of patients were also collected. Only 1/755 MS patients exhibited the premutation expansion with a heterozygosis pattern (30/58). No pathogenic repeat expansions (>200 repeats) were found in the entire cohort. Repeats labeled as the gray zone (45-60 repeats) were observed in 15/755 patients. No specific clinical features concerning disease course, disease activity, and disability were reported for these patients. Our results do not support a possible role for premutation or gray zone alleles in MS Sardinian patients. Further studies are needed to better understand the relationship between FXTAS and MS.

Spinal cord MRI activity in multiple sclerosis: Predictive value for relapses and impact on treatment decisions.

INTRODUCTION: Emerging evidence suggests the prognostic value of spinal cord (SC) pathology in multiple sclerosis (MS). However, the 2021 MAGNIMS-CMSC-NAIMS guidelines don't recommend routine SC MRI for disease monitoring. This study investigates the frequency of new asymptomatic and isolated SC lesions, exploring their potential to predict clinical activity and guide treatment decisions. METHODS: We enrolled relapsing-remitting MS (RRMS) patients who underwent brain and SC MRI at baseline and after 12 months. New, enlarged, or gadolinium-enhanced (Gd+) lesions on MRI were considered disease activity markers. Clinical relapses and treatment changes observed 3 months after the 12-month MRI were analyzed using regression analysis, evaluating their association with worsening SC findings. RESULTS: A total of 201 RRMS patients (56 males, 27.9%, mean age 42.5 ± 12.1 years, mean EDSS 2.7 ± 1.9) were included. Isolated worsening of T2 lesion burden in the SC occurred in 16 patients (8%), and 12 (6%) had Gd + lesions. Among patients without brain MRI activity (n = 138), regression analysis revealed a significant association between new Gd + SC lesions and clinical relapses within 3 months of the 12-month MRI (p = 0.024). Worsening SC findings (p = 0.021) and SC lesion enhancement (p = 0.046) emerged as key factors influencing disease-modifying therapy changes within 3 months in these patients. Notably, even without clinical symptoms, worsening SC findings significantly predicted treatment changes (p = 0.003). CONCLUSION: Our findings highlight the independent value of SC MRI findings in MS monitoring. Importantly, isolated and asymptomatic SC worsening significantly impacted treatment decisions.

Mycobacterium avium subsp. paratuberculosis and multiple sclerosis in Sardinian patients: epidemiology and clinical features.

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) is an infectious factor recently found in association with multiple sclerosis (MS) in Sardinia. OBJECTIVES: The objectives of this study were to confirm this association and evaluate its role in clinical features. METHODS: A total of 436 patients and 264 healthy controls (HCs) were included. We examined the blood of each individual for MAPDNA and MAP2694 antibodies using IS900-specific PCR and ELISA, respectively. Differences in MAP presence between the MS group and HCs were evaluated. In MS patients, we considered: gender, age, age at onset, duration of disease, course, EDSS, therapy, relapse/steroids at study time, and oligoclonal bands (OBs). RESULTS: MAPDNA and MAP2694 antibodies were detected in 68 MS and six HCs (p = 1.14 × 10(-11)), and 123 MS and 10 HCs (p = 2.59 × 10(-23)), respectively. OBs were found with reduced frequency in MAP-positive patients (OR = 0.52; p = 0.02). MAP2694 antibodies were detected more in patients receiving MS treatments (OR = 2.26; p = 0.01), and MAPDNA in subjects on steroids (OR = 2.65; p = 0.02). CONCLUSION: Our study confirmed the association of MAP and MS in Sardinia. The low OB frequency in MAP patients suggests a peripheral role as a trigger in autoimmunity. MAP positivity might be influenced by steroids and MS therapy. Studies in other populations are needed to confirm the role of MAP in MS.

How to measure the treatment response in progressive multiple sclerosis: Current perspectives and limitations in clinical settings'.

New treatment options are available for active progressive multiple sclerosis (MS), including primary and secondary progressive forms. Several pieces of evidence have recently suggested a "window of beneficial treatment opportunities," principally in the early stages of progression. However, for progressive MS, which is characterised by an inevitable tendency to get worse, it is crucial to redefine the "response to treatment" beyond the concept of "no evidence of disease activity" (NEDA-3), which was initially conceived to evaluate disease outcomes in relapsing-remitting form, albeit it is currently applied to all MS cases in clinical practice. This review examines the current perspectives and limitations in assessing the effectiveness of DMTs and disease outcomes in progressive MS, the current criteria applied in defining the response to DMTs, and the strengths and limitations of clinical scales and tools for evaluating MS evolution and patient perception. Additionally, the impact of age and comorbidities on the assessment of MS outcomes was examined.

Multidimensional frailty and its association with quality of life and disability: A cross-sectional study in people with multiple sclerosis.

BACKGROUND: People with multiple sclerosis (pwMS) have a high risk of frailty. We aim to evaluate frailty using the Tilburg frailty indicator (TFI), a multidimensional self-reported questionnaire, and to explore its relationship with autonomy, quality of life (QoL), and disability. METHODS: All the patients with MS enrolled completed TFI (frail when TFI score ≥ 5 points), the Groningen Activities Restriction Scale to evaluate autonomy, and the Multiple Sclerosis Impact Scale-29 to evaluate QoL. We collected the Expanded Disability Status Scale (EDSS) score, age and gender. Data were analysed using descriptive analyses, hierarchical multiple regression, and ANCOVA. RESULTS: A total of 208 pwMS (mean age 44 years, SD=11; 75% women; 89.4% relapsing-remitting) were enrolled. The mean TFI total score was 5.7 points (SD=3.0; range 0-14), with the 62.5% of participants exhibiting frailty. After controlling for age and gender, the EDSS score was associated with the total (ß=0.469; R2=0.255; p<0.001) and the physical (ß=0.571; R2=0.349; p<0.001) frailty score, with an explained variance of 25.5% and 34.9%, respectively. No relationships between the EDSS and psychological and social frailty domains were detected. The proportion of frail patients with EDSS ≥ 6.0, EDSS within 3.5-5.5, and EDSS ≤ 3.0 was 91.7%, 83.3%, and 66.0%, respectively. Frail patients exhibited higher autonomy impairment (p = 0.017) and worse QoL (p<0.001). DISCUSSION: We found a high frequency of frail patients with MS. Frailty is more common in patients with higher disability, but it affects also those with low EDSS. In people with MS frailty could be influenced by factors other than disability.

Leukocyte telomere length in women with multiple sclerosis: Comparison with healthy women during pregnancy and puerperium.

OBJECTIVES: Several studies indicated leukocyte telomere length (LTL) as a biomarker of multiple sclerosis (MS) evolution. This study aimed to investigate LTL in women with multiple sclerosis (MS) compared to that in healthy women (HW) across different reproductive phases, and to evaluate its relationship with MS activity. METHODS: Blood samples were collected from women with MS and HW during the fertile phase, pregnancy, and puerperium. LTL was determined using quantitative fluorescence in situ hybridization (Q-FISH). RESULTS: Blood samples from 68 women with MS (22 during fertile life, 23 during pregnancy, and 23 post-partum) and 52 HW (23 during fertile life, 20 during pregnancy, and 9 post-partum) were analyzed. During pregnancy, LTL in MS women and HW was 84.7 ± 10.5 and 77.6 ± 11.5, respectively (p < 0.005). Regression analysis showed that shorter LTL was associated with pregnancy in HW (p = 0.021); this relationship was not observed in MS women, for whom shorter LTL was related to a higher EDSS (p = 0.036). A longitudinal analysis was performed in eight MS women, showing LTL shortening from pregnancy to puerperium (p = 0.003), which was related to MS reactivation (p = 0.042). CONCLUSION: Our results highlight the possible associations between LTL, reproductive biological phases, and MS activity after delivery.

Spatial genetic structure of Aquilegia taxa endemic to the island of Sardinia.

BACKGROUND AND AIMS: The Mediterranean Basin is one of the most important regions for the Earth's plant biodiversity; however, the scarcity of studies on fine scale patterns of genetic variation in this region is striking. Here, an assessment is made of the spatial genetic structure of all known locations of the three Sardinian endemic species of Aquilegia in order to determine the relative roles of gene flow and genetic drift as underlying evolutionary forces canalizing the divergence of Sardinian Aquilegia taxa, and to see if the spatial genetic structure found fits the current taxonomic differentiation of these taxa. METHODS: DNA from 89 individuals from all known locations of Aquilegia across Sardinia was analysed by means of amplified fragment length polymorphism (AFLP) markers. Both principal co-ordinates analysis (PCoA) and Bayesian clustering analyses were used to determine the spatial genetic structure irrespective of any taxonomic affiliation. Historical effects of gene flow and genetic drift were assessed by checking for the existence of isolation-by-distance patterns. KEY RESULTS: STRUCTURE and PCoA analyses revealed a pattern of genetic variation geographically structured into four spatial genetic groups. No migration-drift equilibrium was detected for Aquilegia in Sardinia, when analysed either as a whole or in individual groups. The scenario approached a Case III pattern sensu Hutchinson and Templeton, which is associated with extreme isolation conditions where genetic drift has historically played a dominant role over gene flow. CONCLUSIONS: The pattern of genetic variation of Sardinian taxa of Aquilegia indicates that genetic drift has been historically more influential than gene flow on population structure of Sardinian species of Aquilegia. Limited seed dispersal and divergent selection imposed by habitat conditions have been probably the main causes reinforcing post-Pleistocene geographical isolation of Aquilegia populations. The spatial genetic structure found here is not fully compatible with current taxonomic affiliations of Sardinian Aquilegia taxa. This is probably a consequence of the uncoupling between morphological and genetic patterns of differentiation frequently found in recently radiated taxa.

Evolution of teriflunomide use in multiple sclerosis: A real-world experience.

OBJECTIVES: The present study aims to describe the evolution of teriflunomide use for multiple sclerosis (MS) in the clinical setting, in particular for naïve patients and young women. Predictors of treatment response were also investigated. METHODS: This was an independent, retrospective, real-world monocentric study. We analysed the use of teriflunomide from 2016 to 2020 in patients categorized as naïve or switchers, and assessed the variations in its use in men and women by age group. Clinical and MRI data of treated patients were evaluated, and NEDA-3 status at 24 and 36 months was defined. Determinants of therapeutic response were examined using regression analysis. RESULTS: The study included 319 MS patients exposed to teriflunomide [209 women (65.5%)]. Of these, 67 (21%) were naïve and 252 (79%) were switchers. A 20% increase of teriflunomide use in the naïve group in the past two years, particularly in 2020, the first year of global Sars-Cov-2 spread, was observed. An increase of teriflunomide use of more than 10% in young women under age 45 was also reported. NEDA-3 status was calculated for 204 patients after 24 months and was achieved in 120 (58.8%) of these ones. NEDA-3 was also achieved in 92/160 (56.8%) patients at 36 months. A lower ARR in the two years prior to teriflunomide treatment (p = 0.026), lower baseline age (p = 0.05), and lower EDSS score (p = 0.009) were associated with achievement of the NEDA-3. CONCLUSIONS: Our study confirms a major evolution in teriflunomide use in clinical settings, particularly for naïve patients and young women.

The cohort of the multiple sclerosis center of Cagliari.

We report our experience in long-term treatment of relapsing remitting multiple sclerosis patients with natalizumab (N). In November 2009 we evaluated 141 patients (126 AIFA criterion A, 15 AIFA criterion B). We paid particular attention to the treatment period and the patients follow-up; during the whole therapeutic program, they undergone to clinical and radiological evaluation for every 3 months. The compliance was optimal and we found no significant side effects. 26 patients completed the 24 monthly doses. After 24 months 51% of patients were free from disease activity. We found a reduction in relapses and EDSS, moreover the clinical improvement was also confirmed by radiological examinations. Our results show that the best therapeutic results are achieved by early initiation of treatment.

Event-related potentials and deep grey matter atrophy in multiple sclerosis: Exploring the possible associations with cognition.

BACKGROUND: Event-related potentials (ERPs) have been proposed as a neurophysiological biomarker to capture cognitive dysfunction in multiple sclerosis (MS). Few studies have evaluated the relationships between ERPs and brain atrophy as known marker of structural brain damage related to cognitive impairment (CI). OBJECTIVES: To explore the relationships of brain atrophy, including of the cortex and deep grey matter, with ERP abnormalities and cognitive function, as defined using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). RESULTS: Seventy-eight patients with relapsing-remitting MS were enroled, of which 38 (48.7%) had CI. Independent t-test comparisons of the ERP parameters found a significant difference in P300 wave latency, with a latency of 343.7 ± 32.6 ms in the CI group vs. 320.3 ± 16.5 ms in the cognitively preserved (CP) group (p = 0.001). Significant differences in the MRI measurements, including the cortex (p = 0.02) and deep grey matter structures [thalamus (p = 0.001), amygdala (p = 0.030), and nucleus accumbens (p = 0.004)) were observed, with lower measurements in the CI group. Regression models were also performed to explore the impact of brain volumes on ERP parameters. This showed a relationship between P300 latency and the lower amygdala (p = 0.02) and hippocampus (p = 0.03) volumes, while the amplitude of the P300 was significantly associated with a lower cortex volume (p = 0.01). CONCLUSION: Cortex volume emerged as the most significant predictor of the P300 amplitude. The amygdala and hippocampal volumes were found to influence P300 latency, highlighting the role of deep grey matter atrophy in ERPs for the first time. The combination of structural MRI and neurophysiological techniques, sensitive to diverse aspects of MS pathology, could improve the understanding of CI in MS and its neurodegenerative and inflammatory substrate.

Bipolar disorders and deep grey matter in multiple sclerosis: A preliminary quantitative MRI study.

BACKGROUND: Bipolar disorder (BD) is frequently observed in patients affected by multiple sclerosis (MS), presenting a lifetime estimate of around 8%. However, uncertainty exists on the brain damage associated with this psychiatric comorbidity. This study aimed to investigate the effect of brain atrophy, particularly that of the subcortical grey matter (scGM) structures that notoriously regulate the affective functioning, on the co-occurrence of BD in patients with MS. METHODS: A group of patients with MS affected by BD and a control group of patients with MS without any mood/psychiatric disorder, as defined using standardised diagnostic tools (Advanced Neuropsychiatric Tools and Assessment Schedule), were recruited. The patients underwent brain MRI, and the volumes of the whole brain (WB), white matter (WM), and grey matter (GM) were estimated using SIENAX. Thus, the scGM volumes of the putamen, caudate, thalamus, hippocampus, amygdala, nucleus accumbens, and pallidus were estimated using the FIRST tool. RESULTS: The sample included 61 patients with MS, amongst whom 15 (24.6%) had BD. No differences in the WB, WM, and cortical GM volumes were observed between the patients with MS with and without BD. Conversely, the multiple regression analysis revealed a significant association of BD with lower volumes of the putamen (p = 0.032), nucleus accumbens (p = 0.029), and pallidus (p = 0.061; with a trend towards significance), independently from the demographic and MS clinical features. CONCLUSIONS: Our preliminary results indicated that the nucleus accumbens and putamen are smaller in MS patients with BD. Further investigations in larger cohorts of MS patients with affective disorders are necessary to confirm these data and understand the structural brain damage underlying this psychiatric comorbidity.

The impact of deep grey matter volume on cognition in multiple sclerosis.

BACKGROUND: Cognitive dysfunctions are very frequent in people living with multiple sclerosis (MS). Several studies have previously indicated grey matter (GM) atrophy as useful predictor of patients' cognitive impairment. However, considerable uncertainty exists about the possible impact of deep grey matter volumes on cognition. This study aimed to evaluate the relationship of the subcortical (sc) GM volumes with the presence and severity of global and selective cognitive impairment in MS. METHODS: A group of MS patients with relapsing remitting course were enrolled. Patients underwent a neuropsychological evaluation by using the Brief Repeatable Battery of Neuropsychological Tests (BRBN) and the Delis-Kaplan Executive Function System Sorting Test (D-KEFST); z scores were estimated and items with z score below 2 standard deviation were considered failed. Thus, brain MRIs images were acquired and measurements of whole brain (WB), white matter (WM), and cortical grey matter (GM) were obtained by SIENAX. After FIRST tool segmentation, volumes of subcortical GM structures were also estimated. RESULTS: The sample included 50 MS patients, of which 16/50 (32%) subjects were cognitively impaired. Multiple regression analyses found a significant association of severity of cognitive impairment, defined as number of failed neuropsychological tests, with lower volumes of cortex (p=0.003), thalamus (p=0.009), caudate (p=0.011), putamen (p=0.020), pallidus (p=0.012) and hippocampus (p=0.045), independently from other MS features. In addition, an association between accumbens volume and D-KEFS ST FSC and D-KEFS ST FSD z scores was observed (p<0.03). CONCLUSIONS: Our results indicated that volumes of several scGM structures, and in particular of thalamus, contribute to determine cognitive dysfunctions in MS, mainly influencing the executive functioning. Further investigations in larger MS cohorts with cognitive impairment are necessary to better understand the structural brain damage underlying this "invisible disability".

Is vegetation an indicator for evaluating the impact of tourism on the conservation status of Mediterranean coastal dunes?

Mediterranean coastal dunes are threatened by several factors; particularly, tourism causes modifications to the vegetation and the disappearance of endemic species. Understanding the dunes' conservation status is crucial for preserving these vulnerable environments through appropriate management strategies. This study was conducted on 17 Sardinian coastal dunes, with different levels of touristic pressure. We focused on endemic plant species and developed a new endemicity index (EI). Our study aimed: 1) to assess the conservation status by applying the diversity indices; 2) to verify if the study sites would reveal a general pattern based on different degrees of human disturbance and 3) to test the effectiveness of the EI index. Four m2 plots (2 × 2 m) were placed along orthogonal transects to the coastline (446 plots in total), in which all plant species were identified, and their relative abundance was estimated. We found significant differences among the sites for Hdune and EI values but no statistically significant differences in the N values. The EI showed the high naturalistic value of Sardinian coastal dunes and allowed us to distinguish the sites with higher anthropic pressure. We found significant differences in the indices among the degrees of human disturbance in the coastal systems. The Hdune values were positively related to a medium level of human disturbance, and the EI allowed us to distinguish the sites with varying levels of human disturbance, although it differentiated better those with the highest anthropic pressure. A medium level of human disturbance was positively related to the plant richness and cover, and human trampling could be tolerated by psammophilous vascular plants. Results showed a satisfactory conservation status of Sardinian dune systems and highlighted diversity indices as valuable support for implementing a conservation strategy, compatible with the tourism purposes and the integrated management of the Mediterranean coastal dune systems.

Assessing the burden of vascular risk factors on brain atrophy in multiple sclerosis: A case- control MRI study.

BACKGROUND: Some studies have indicated the importance of considering the presence of vascular comorbidities as negative prognostic factors for MRI outcomes in multiple sclerosis (MS). This study aimed to evaluate the possible influence of the most frequent vascular risk factors on brain volume in MS, also exploring the burden of their combined effects. METHODS: MS patients with at least one vascular risk factor and a control group of MS patients were enrolled. Patients underwent brain MRI and the volumes of the whole brain (WB), white matter (WM), grey matter (GM), and cortical GM were estimated by SIENAX. Longitudinal atrophy was assessed by SIENA. RESULTS: The sample included 326 MS patients, of these 49 (15%) had diabetes mellitus, 44 (13.4%) hypertension and 50 (15.3%) were active smokers. Multiple regression analyses revealed that diabetes mellitus was associated with significant reductions in WB (p = 0.03), GM and cortical GM (p = 0.01) volumes. Similarly, reduced cortical GM volume was associated with hypertension (p < 0.05). A strong relationship between the co-occurrence of multiple vascular risk factors and lower cortical GM volume (p = 0.007) was also identified. Ninety patients were included in the longitudinal study and a greater annualized brain volume loss was found in those with at least one vascular risk factor than in the control group (-1.05% vs. -0.58%, p = 0.005). CONCLUSIONS: Our results show that the vascular comorbidities affect brain atrophy, indicating that these conditions should be carefully monitored in patients with MS with a focus on limiting brain damage.