Informing MS patients on treatment options: a consensus on the process of consent taking.

In the last years, change in multiple sclerosis (MS) therapeutic scenario has highlighted the need for an improved doctor-patient communication in advance of treatment initiation in order to allow patient's empowerment in the decision-making process. AIMS: The aims of our project were to review the strategies used by Italian MS specialists to inform patients about treatment options and to design a multicentre shared document that homogenizes the information about disease-modifying treatment (DMTs) and the procedure of taking informed consent in clinical practice. RESULTS: The new resource, obtained by consensus among 31 neurologists from 27 MS Centres in Italy with the supervision of a medico-legal advisor, received the aegis of Italian Neurological Society (SIN) and constitutes a step toward a standardized decision process around DMTs in MS.

Retinal vascular density in multiple sclerosis: a 1-year follow-up.

BACKGROUND AND PURPOSE: Vascular pathology is increasingly acknowledged as a risk factor for multiple sclerosis (MS). Vascular density (VD) is reduced in the eyes of patients with MS on optical coherence tomography (OCT) angiography. We performed a 1-year prospective study to estimate VD variations over time and possible clinical correlates. METHODS: A total of 50 patients with MS underwent spectral domain-OCT and OCT angiography at baseline and after 1-year follow-up. Mixed-effect linear regression models were used to assess variations of each OCT measure and its relation to treatment and clinical outcomes. RESULTS: We observed an increase in parafovea VD (coefficient, 1.147; 95% confidence interval, 0.081-2.214; P = 0.035). Reduction in parafovea VD was associated with increase in Expanded Disability Status Scale score (coefficient, -0.969; 95% confidence interval, -1.732/-0.207; P = 0.013). CONCLUSIONS: Retinal VD can improve over time in MS, particularly in patients experiencing disease stability. Longer follow-up, inclusion of early MS cases and combination with conventional markers of MS severity (i.e. brain atrophy) are needed to better define VD as a potential new biomarker.

Grey:white matter ratio at diagnosis and the risk of 10-year multiple sclerosis progression.

BACKGROUND AND PURPOSE: Grey matter (GM) and white matter (WM) are both affected in multiple sclerosis (MS). WM is predominantly involved in inflammatory demyelination of relapsing-remitting MS (RRMS), whereas GM is predominantly involved in neurodegenerative processes of secondary progressive MS. Thus, we investigated the ratio between GM and WM volumes in predicting MS evolution. METHODS: The present 10-year retrospective cohort study included 149 patients with newly-diagnosed RRMS, undergoing magnetic resonance imaging for segmentation and brain volumetry. The ratio between GM and normal-appearing WM (NAWM) volumes was calculated for each subject. Outcome measures of interest were Expanded Disability Status Scale (EDSS) progression, reaching EDSS 4.0 and conversion to secondary progressive (SP) MS. RESULTS: During a period of 10.6 ± 2.4 years, a median 1.5 EDSS progression was observed (range 0-5.5), 54 subjects (36.2%) reached EDSS 4.0 and 30 subjects (20.1%) converted to SP. With ordinal logistic regression models, EDSS progression was associated with GM:NAWM ratio (coefficient, -2.918; 95% CI, -4.739-1.097). With Cox regression models, subjects with higher GM:NAWM ratio at diagnosis had a 90% lower rate of reaching EDSS 4.0 (hazard ratio, 0.111; 95% CI, 0.020-0.609) and of converting to secondary progressive MS (hazard ratio, 0.017; 95% CI, 0.001-0.203) compared with subjects with lower GM:NAWM ratio. CONCLUSIONS: The GM:NAWM ratio is a predictor of disability progression and of SP conversion in subjects with newly diagnosed RRMS, suggesting that GM and NAWM are variably affected in relation to disease evolution from the early phases of MS.

Growth hormone/IGF-1 axis longitudinal evaluation in clinically isolated syndrome patients on interferon ß-1b therapy: stimulation tests and correlations with clinical and radiological conversion to multiple sclerosis.

BACKGROUND AND PURPOSE: Growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis abnormalities in multiple sclerosis (MS) suggest their role in its pathogenesis. Interferon ß (IFN-ß) efficacy could be mediated also by an increase of IGF-1 levels. A 2-year longitudinal study was performed to estimate the prevalence of GH and/or IGF-1 deficiency in clinically isolated syndrome (CIS) patients and their correlation with conversion to MS in IFN treated patients. METHODS: Clinical and demographic features of CIS patients were collected before the start of IFN-ß-1b. IGF-1 levels and GH response after arginine and GH releasing hormone + arginine stimulation tests were assessed. Clinical and magnetic resonance imaging evaluations were performed at baseline, 1 year and 2 years. RESULTS: Thirty CIS patients (24 female) were enrolled. At baseline, four patients (13%) showed a hypothalamic GH deficiency (GHD), whilst no one had a pituitary GHD. Baseline demographic, clinical and radiological data were not related to GHD, whilst IGF-1 levels were inversely related to age (P < 0.001) and GH levels (P = 0.03). GH and IGF-1 serum mean levels were not significantly modified after 1 and 2 years of treatment in the whole group, although 3/4 GHD patients experienced a normalization of GH levels, whilst one dropped out. After 2 years of treatment 13/28 (46%) patients converted to MS. The presence of GHD and GH and IGF-1 levels were not predictive of relapses, new T2 lesions or conversion occurrence. CONCLUSIONS: Growth hormone/IGF-1 axis function was found to be frequently altered in CIS patients, but this was not related to MS conversion. Patients experienced an improvement of GHD during IFN therapy. Longer follow-up is necessary to assess its impact on disease progression.

Predictors of the 10-year direct costs for treating multiple sclerosis.

OBJECTIVES: Disease-modifying treatments (DMTs) constitute the largest direct medical cost for multiple sclerosis (MS). This study aims at investigating predictors of the 10-year economic burden for DMT administration and management. MATERIALS AND METHODS: This study included 537 newly diagnosed, drug naïve relapsing-remitting MS (RRMS) patients, followed up for 10.1±3.3 years. Costs for DMT administration and management were calculated, and referred to each year of observation (annual costs). Possible predictors of disease evolution were categorized into early predictors (age, gender, disease duration, baseline expanded disability status scale (EDSS), 1-point EDSS progression within 2 years, and annualized relapse rate -ARR- within 2 years), and long-term predictors (reaching of EDSS 4.0, conversion to secondary progressive -SP-, ARR, number of DMTs, follow-up duration). Association between predictors and study outcome was explored using mixed-effects log-linear regression models. RESULTS: A 1-point higher EDSS at diagnosis was associated with 13.21% increase in the annual costs (95%CI=4.16-23.04%). Each additional year of age at diagnosis was associated with a 0.74% decrease in the annual costs (95%CI=-1.43 to-0.04%). Female gender was associated with a 12.43% decrease in the annual costs (95%CI=-22.61 to-0.93%). Converting to SP was associated with a 14.26% decrease in the annual costs (95%CI=-14.26 to-2.94%). Each additional year of follow-up was associated with a 3.05% decrease in the annual costs (95%CI=-4.51 to-1.57%). CONCLUSIONS: An estimate of the 10-year costs associated with DMT administration and management can be calculated by analyzing different factors, and might be of particular interest for planning resources needed for treating people with MS.

A longitudinal real-life comparison study of natalizumab and fingolimod.

BACKGROUND: Different retrospective studies compared natalizumab and fingolimod in relapsing-remitting multiple sclerosis (RRMS), with conflicting results. We aimed to explore the prescriptive attitude and the clinical outcome of the two therapies. METHODS: We retrospectively included all RRMS patients treated with natalizumab (n=101) or fingolimod (n=78) as their first second-line therapy with at least 24-month follow-up. Demographic and clinical features were recorded to calculate the propensity score (PS). Outcomes of interest were annualized relapse rate (ARR), risk of relapse, and change in the EDSS RESULTS: At baseline, natalizumab patients were younger and had a shorter disease duration, a higher number of relapse in 1 year (1yR) and 2 years (2yR) and overall (ARR-PT) pretherapy, compared to fingolimod patients. On therapy, the proportion of relapsing patients and the mean RR were similar in the two groups. However, the change in the ARR was higher in natalizumab than in fingolimod group (P<.002), but, using PS as a covariate, it was comparable (P=.960). Similarly, the change in EDSS was significantly different for the two groups (P<.004), but not after adjusting for the PS (P=.321). CONCLUSION: We observed a comparable efficacy on ARR reduction and on EDSS progression with natalizumab and fingolimod correcting through PS, suggesting that the efficacy difference observed before correction might derive from the clinical attitude in prescribing natalizumab in more active MS patients in real life.

The non-motor side of the honeymoon period of Parkinson's disease and its relationship with quality of life: a 4-year longitudinal study.

BACKGROUND AND PURPOSE: Very little is known about the progression of non-motor symptoms (NMSs) in Parkinson's disease (PD) and there are no longitudinal studies exploring this topic from the earliest stage, when patients receive the diagnosis. We here report on the progression of NMSs over 4 years from diagnosis in a cohort of de-novo, previously untreated, patients with PD. METHODS: Consecutive de-novo (disease duration < 2 years), untreated patients with PD were enrolled in this observational study. Evaluations were then scheduled every 2 years and included assessment of motor and non-motor features as well as of quality of life measures. RESULTS: Sixty-one patients were prospectively followed-up for 4 years from diagnosis. The majority of NMSs increased over time and significantly affected quality of life, whereas motor disability did not. There was no significant association between NMSs and dopaminergic therapy in terms of both drug class and total levodopa-equivalent daily dosage. Excessive daytime sleepiness was the only NMS correlating with therapy with dopamine agonists. Female patients were more likely to have worse quality of life. CONCLUSIONS: Non-motor symptoms significantly increase over time, with a different progression rate for each one. NMSs significantly affect quality of life in PD and we here demonstrated that this was especially the case when patients were in their (motor) honeymoon period. Future trials should target non-dopaminergic networks and consider NMSs in their outcomes.

Presence and progression of non-motor symptoms in relation to uric acid in de novo Parkinson's disease.

BACKGROUND AND PURPOSE: Uric acid (UA) has been studied extensively as a valuable biomarker of Parkinson's disease (PD), but its relationship with non-motor symptoms (NMS) in de novo PD has been poorly investigated. Our aim was to evaluate the usefulness of baseline serum UA as a marker of NMS progression in newly diagnosed PD. METHODS: Sixty-nine newly diagnosed PD patients were enrolled. At baseline, all patients completed the NMS questionnaire (NMSQuest), and serum UA levels were measured. After 2 years, the NMSQuest was completed again and patients were categorized into four groups: NMS improvement (domain involvement at baseline but not at 2-year follow-up visit), NMS absence (domain not involved at baseline or 2-year follow-up visits), NMS presence (domain involvement both at baseline and 2-year follow-up visits) and NMS worsening (domain not involved at baseline but involved at 2-year follow-up). RESULTS: ANOVA with post hoc Bonferroni correction showed that patients with NMS absence presented significantly higher UA values than patients with NMS presence with regard to the attention/memory (P = 0.023), depression/anxiety (P = 0.028) and cardiovascular domains (P = 0.002), whilst no differences were found with regard to both the NMS improvement and worsening groups. In addition, multinomial regression analysis showed that the lowest tertile of NMS progression presented higher UA levels (P = 0.023; odds ratio 0.488) compared with patients with greater NMS progression. CONCLUSIONS: This is the first report of a relationship between serum UA and presence/progression of multiple NMS in de novo PD, providing additional evidence of the reliability of UA as a biomarker of PD and opening new insights on PD neuroprotection.

The Framingham cardiovascular risk score in multiple sclerosis.

BACKGROUND AND PURPOSE: Cardiovascular risk factors can increase the risk of multiple sclerosis (MS) and modify its course. However, such factors possibly interact, determining a global cardiovascular risk. Our aim was to compare the global cardiovascular risk of subjects with and without MS with the simplified 10-year Framingham General Cardiovascular Disease Risk Score (FR) and to evaluate its importance on MS-related outcomes. METHODS: Age, gender, smoking status, body mass index, systolic blood pressure, type II diabetes and use of antihypertensive medications were recorded in subjects with and without MS to estimate the FR, an individualized percentage risk score estimating the 10-year likelihood of cardiovascular events. RESULTS: In total, 265 MS subjects were identified with 530 matched controls. A t test showed similar FR in cases and controls (P = 0.212). Secondary progressive MS presented significantly higher FR compared to relapsing-remitting MS (P < 0.001). Linear regression analysis showed a direct relationship between FR and Expanded Disability Status Scale (P < 0.001) and MS Severity Scale (P < 0.001). CONCLUSION: The FR, evaluating the global cardiovascular health by the interaction amongst different risk factors, relates to MS disability, severity and course.

Increased bilirubin levels in de novo Parkinson's disease.

BACKGROUND AND PURPOSE: Oxidative stress is a central pathogenic mechanism of Parkinson's disease (PD), and the heme oxygenase (HO) bilirubin pathway is one of the main mammalian antioxidative defences. Indeed, there is growing evidence of HO-bilirubin upregulation from early phases of PD. Our aim was to investigate bilirubin as a possible biomarker of PD diagnosis and progression. METHODS: A cross-sectional case-control study was performed to evaluate differences in bilirubin levels between newly diagnosed, drug-naïve PD subjects and controls. Afterwards, PD subjects were included in a 2-year longitudinal study to evaluate disease progression in relation to baseline bilirubin levels. RESULTS: Seventy-five de novo PD subjects were selected and matched with 75 controls by propensity score. Analysis of variance showed higher bilirubin levels in PD patients compared with controls (P < 0.001). Linear regression analysis failed to show a relationship between bilirubin and Unified Parkinson's Disease Rating Scale (UPDRS) part III (P = 0.283) at baseline evaluation. At 2-year follow-up, indirect relationships between bilirubin levels and UPDRS part III (P = 0.028) and between bilirubin levels and levodopa-equivalent daily dosage (P = 0.012) were found. CONCLUSIONS: Parkinson's disease subjects showed higher levels of bilirubin compared with controls. Bilirubin increase might be due to HO overexpression as a compensatory response to oxidative stress occurring from early stages of PD.

Relationship between apathy and cognitive dysfunctions in de novo untreated Parkinson's disease: a prospective longitudinal study.

BACKGROUND AND PURPOSE: Apathy may be either a symptom of major depression or a behavioral disturbance occurring in concomitance with depression or alone in Parkinson's disease (PD). The aim of the present study was to determine the progression of cognitive impairment in drug-naïve untreated PD patients with or without clinically significant apathy. METHODS: Sixty-two PD patients with a disease duration <2 years and without history of present or past therapy with pro-dopaminergic agents were included and underwent the Apathy Evaluation Scale (S-AES), a clinical interview based on diagnostic criteria for apathy and a comprehensive neuropsychological battery to assess memory, frontal functions and visuospatial functions. Two years after the first assessment, all patients were re-evaluated on the S-AES, a clinical interview and neuropsychological tests. RESULTS: According to the cut-off value of the S-AES and diagnostic criteria for apathy, eight patients experienced apathy at both baseline and follow-up (A+A+), nine patients had apathy only at follow-up (A-A+), 37 patients never experienced apathy (A-A-) and eight patients showed apathy at the baseline only (A+A-). Cognitive performance significantly declined in all four groups. At both baseline and follow-up A+A+ performed worse than A-A- on visuospatial and frontal tests; A-A+ had lower scores than A-A- on the interference task of the Stroop test (IT-ST). Regression analysis showed that poor performance on the IT-ST at baseline was the only independent predictor of onset of apathy at follow-up. CONCLUSIONS: The results indicated a relationship between apathy and dysexecutive syndrome in early PD. Reduced scores on the IT-ST may predict development of apathy in PD patients.

Cognitive performances and DAT imaging in early Parkinson's disease with mild cognitive impairment: a preliminary study.

OBJECTIVES: Mild cognitive impairment (MCI) is a common feature in Parkinson's disease (PD). We performed an exploratory study to investigate dopaminergic nigrostriatal innervation and its cognitive correlates in early untreated PD patients with MCI as compared to cognitively intact patients. PATIENTS AND METHODS: A consecutive series of 34-de-novo, drug-naïve patients with PD were enrolled. They underwent [123-I] FP-CIT SPECT and comprehensive neuropsychological battery. MCI was identified in 15 of 34 patients with PD. RESULTS: The two groups did not show any statistically significant difference in age, sex, disease duration, education, lateralization, and H&Y and Hospital Anxiety and Depression Scale scores. Logistic regression analysis showed that UPDRS-III was weakly associated with MCI (P = 0.034). Partial correlation analysis controlling for UPDRS-III and age suggested that in PD patients with MCI reduced V3″ values in the more affected caudate were correlated with reduced performances in frontal assessment battery, Trail Making Test: part B minus Part A and copy task of the Rey-Osterrieth complex figure test. Reduced V3″ values in the more and less affected putamen were significantly related with reduced performance in frontal assessment battery and in copy task of Rey-Osterrieth complex figure test, respectively. No correlation was found between neuropsychological scores and DAT availability in PD patients without MCI. CONCLUSIONS: Although preliminary, our results suggest that striatal dopamine depletion may contribute to some cognitive deficit in early never treated PD patients with MCI.

Uric acid relates to dopamine transporter availability in Parkinson's disease.

BACKGROUND: Diagnosing Parkinson's disease (PD) and tracking its progression may require the combination of reliable biomarkers. Among them, both serum uric acid (UA) and dopamine transporter (DaT) binding deserve more investigations. AIMS OF THE STUDY: We aimed to investigate the relationship between serum UA levels and DaT availability in newly diagnosed, drug-naïve PD patients, by means of semiquantitative [(123) I]FP-CIT-SPECT. METHODS: We recruited 52 newly diagnosed, drug-naïve PD patients, and performed serum UA dosage and [(123) I]FP-CIT-SPECT. RESULTS: Pearson's correlation analysis showed that UA levels were significantly higher in patients with higher averaged, ipsilateral and contralateral DaT binding in caudate, putamen, and striatum. CONCLUSIONS: We showed, for the first time, by regional semiquantitative analysis of DaT binding in PD patients that UA levels significantly correlates with the severity of dopaminergic impairment in caudate, putamen, and striatum. This study broadens our knowledge on the importance of UA as a biomarker of PD.

Insulin-like growth factor-1 predicts cognitive functions at 2-year follow-up in early, drug-naïve Parkinson's disease.

BACKGROUND AND PURPOSE: Cognitive impairment is common in Parkinson's disease (PD), even in the early stages. We aimed to assess the relationship between insulin-like growth factor-1 (IGF-1) and cognitive functions in early, drug-naïve patients with PD. METHODS: Serum IGF-1 was measured in 65 early, drug-naïve patients with PD that underwent a complete neuropsychological battery at baseline and after 2 years. Linear regression analysis was used to evaluate the relationships between neuropsychological scores and IGF-1. Repeated-measures anova was applied to assess changes in neuropsychological variables over time. RESULTS: At baseline, IGF-1 levels were related to phonological fluency. At follow-up, IGF-1 levels were associated with the Rey auditory verbal learning test (RAVLT) - immediate and delayed recall, Frontal Assessment Battery, verbal span and Benton judgement of the line orientation test. Patients with low IGF-1 levels at baseline showed a significantly faster decline of performances than patients with high IGF-1 levels on immediate and delayed recall of the RAVLT and interference task of the Stroop test. CONCLUSIONS: Low serum IGF-1 levels are related to poor performance on executive tasks in early, drug-naïve patients with PD, and may predict poor performance on attention/executive and verbal memory tasks after a 2-year follow-up.

Utilization of peginterferon-ß-1a in the real-world practice for relapsing-remitting multiple sclerosis.

OBJECTIVE: Peginterferon ß-1a (PEG-IFN-ß-1a) is the most recent interferon beta formulation approved for treating relapsing-remitting multiple sclerosis (RRMS). We aim to describe the real-world utilization of PEG-IFN-ß-1a in RRMS and compare it with other injectable disease-modifying therapies (DMTs). PATIENTS AND METHODS: In this population-based study, we used 2015-2019 routinely collected healthcare data of the Campania region of Italy from National Healthcare System DMT prescriptions, inpatient and outpatient clinical records of hospitals in Campania, and the Federico II University MS clinical registry for a subset of patients. We included individuals with RRMS receiving new prescriptions of PEG-IFN-ß-1a [n=281; age = 38.8±12.3 years; females=70.5%; disease duration = 8.4±8.3 years; Expanded Disability Status Scale (EDSS) at baseline=2.0 (1.0-6.5)], glatiramer acetate [n=751; age = 46.0±11.4 years; females=67.1%; disease duration = 9.8±8.2 years; EDSS=4.0 (1.5-8.5)], and subcutaneous (SC) IFN-ß-1a [n=1,226; age = 39.7±11.7 years; females=66.5%; disease duration = 8.2±6.5 years; EDSS 2.5 (1.5-6.5)]. Adherence [medication possession ratio (MPR)], escalation to more effective DMTs, hospitalization rates and costs were measured. We used mixed-effect linear regression models (for adherence, hospitalization rates and costs) and Cox regression models (for escalation) to assess differences between PEG-IFN-ß-1a (statistical reference), glatiramer acetate, and SC IFN-ß-1a. All models included age, sex, previous treatment/untreated, year of treatment initiation, treatment duration, and adherence as covariates. RESULTS: Adherence was lower in glatiramer acetate (MPR = 0.91±0.1; Coeff=-0.11; p<0.01), and IFN-ß-1a (MPR = 0.92±0.1; Coeff=-0.08; p<0.01), compared with PEG-IFN-ß-1a (MPR = 1.01±0.1). The probability of escalating to more effective DMTs was higher for glatiramer acetate (14.9%; HR=4.09; p<0.01) and IFN-ß-1a (9.1%; HR=3.35; p=0.01), compared with PEG-IFN-ß-1a (4.9%). No differences in annualized hospitalization rates were identified between glatiramer acetate [annualized hospitalization rates (AHR) = 0.05±0.30; Coeff=0.02; p=0.31), IFN-ß-1a (AHR = 0.02±0.21; Coeff=0.01; p=0.97], and PEG-IFN-ß-1a (AHR = 0.02±0.24); however, monthly costs for MS admissions were higher for glatiramer acetate (€49.45±€195.27; Coeff=-29.89; p=0.03), compared with IFN-ß-1a (€29.42±€47.83; Coeff=6.79; p=0.61), and PEG-IFN-ß-1a (€23.91±€43.90). CONCLUSIONS: SC PEG-IFN-ß-1a and IFN-ß-1a were used in relatively similar populations, while glatiramer acetate was preferred in older and more disabled patients. PEG-IFN-ß-1a was associated with higher adherence and lower escalation rates toward more effective (and costly) DMTs.

Author Correction: Utilization of peginterferon-ß-1a in the real-world practice for relapsing-remitting multiple sclerosis.

Correction to: European Review for Medical and Pharmacological Sciences 2024; 28 (1): 411-418. DOI: 10.26355/eurrev_202401_34930-published online on January 16, 2024. After publication, the authors have applied some corrections to the galley proof: • In the Patients and Methods section of the abstract, "National Health System" is corrected to "National Health Service". • In the Conclusions section of the abstract, "SC PEG-IFN-ß-1a and IFN- ß-1a" is corrected to "PEG-IFN-ß-1a and SC IFN-ß-1a". • In the Population section, the study period "January 1st 2015 to December 31st 2019" was not reported; therefore, this specification has been added to the text. • The legend of Figure 1 was wrongly reported as the same as Table I. The correct title of Figure 1 is "Study flow diagram". • Under Tables I, II, and III, "interferon beta 1a IFN-ß-1a" is corrected to "interferon beta 1a (IFN-ß-1a)". • In Table III, "CS Glatiramer acetate" is corrected to "SC Glatiramer acetate". • In the Conclusions section, "SC IFN-ß-1a SC" is corrected to "SC IFN-ß-1a". • The funding section has been amended as follows: "This study was sponsored by Biogen Italia (Milan, Italy)." There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34930.

MR Imaging Signs of Gadolinium Retention Are Not Associated with Long-Term Motor and Cognitive Outcomes in Multiple Sclerosis.

BACKGROUND AND PURPOSE: The long-term impact of gadolinium retention in the dentate nuclei of patients undergoing administration of seriate gadolinium-based contrast agents is still widely unexplored. The aim of this study was to evaluate the impact of gadolinium retention on motor and cognitive disability in patients with MS during long-term follow-up. MATERIALS AND METHODS: In this retrospective study, clinical data were obtained from patients with MS followed in a single center from 2013 to 2022 at different time points. These included the Expanded Disability Status Scale score to evaluate motor impairment and the Brief International Cognitive Assessment for MS battery to investigate cognitive performances and their respective changes with time. The association with qualitative and quantitative MR imaging signs of gadolinium retention (namely, the presence of dentate nuclei T1-weighted hyperintensity and changes in longitudinal relaxation R1 maps, respectively) was probed using different General Linear Models and regression analyses. RESULTS: No significant differences in motor or cognitive symptoms emerged between patients showing dentate nuclei hyperintensity and those without visible changes on T1WIs (P = .14 and 0.92, respectively). When we tested possible relationships between quantitative dentate nuclei R1 values and both motor and cognitive symptoms, separately, the regression models including demographic, clinical, and MR imaging features explained 40.5% and 16.5% of the variance, respectively, without any significant effect of dentate nuclei R1 values (P = .21 and 0.30, respectively). CONCLUSIONS: Our findings suggest that gadolinium retention in the brains of patients with MS is not associated with long-term motor or cognitive outcomes.

Sexual dysfunction in multiple sclerosis: The impact of different MSISQ-19 cut-offs on prevalence and associated risk factors.

BACKGROUND: Although multiple sclerosis (MS) Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a widely applied tool, no unique definition of sexual dysfunction (SD) based on its score exists. OBJECTIVE: To explore the impact of different MSISQ-19 cut-offs on SD prevalence and associated risk factors, providing relevant information for its application in research and clinical settings. METHODS: After defining SD according to two different MSISQ-19 cut-offs in 1155 people with MS (pwMS), we evaluated SD prevalence and association with sociodemographic and clinical features, mood status and disability via logistic regression. RESULTS: Depending on the chosen cut-off, 45% to 54% of pwMS reported SD. SD defined as MSISQ-19 score >30 was predicted by age (OR=1.01, p=0.047), cognition (OR=0.96, p=0.004) and anxiety (OR=1.03, p=0.019). SD defined as a score >3 on any MSISQ-19 item was predicted by motor disability (OR=1.12, p=0.003) and cognition (OR= 0.96, p=0.002). CONCLUSION: Applying different MSISQ-19 cut-offs influences both the estimated prevalence and the identification of risk factors for SD, a finding that should be considered during study planning and data interpretation. Preserved cognition exerts a protective effect towards SD regardless from the specific study setting, representing a key point for the implementation of preventive and therapeutic strategies.

Risk of invasive fungal infections among patients treated with disease modifying treatments for multiple sclerosis: a comprehensive review.

Introduction: Disease modifying treatments are commonly used in the treatment of multiple sclerosis. As different opportunistic infections have been reported, concerns are also raised regarding the risk of invasive fungal infections.Areas covered: Both clinical trials and observational studies on safety and efficacy of diseases modifying treatment for multiple sclerosis were reviewed and data regarding the occurrence of invasive fungal infections were reported. Papers evaluating the following drugs were reviewed: rituximab, ocrelizumab, alemtuzumab, fingolimod, natalizumab, dimethyl fumarate, interferon, glatiramer acetate, cladribine, teriflunomide.Expert opinion: Overall, the occurrence of invasive fungal infections was low, with most infective events reported among patients treated with monoclonal antibodies and fingolimod. Aspergillosis and cryptococcal meningitidis were the most representative fungal infections. Although not common, these infections may be difficult to diagnose and their fatality rate is often high. For this reason, screening protocols for fungal infections must be implemented in the clinical practice when managing patients with MS.