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Objectives The clinical impact of brain microstructural abnormalities in multiple sclerosis (MS) remains elusive. We aimed to characterize the topography of longitudinal relaxation rate (R1) and quantitative susceptibility (χ) changes, as indices of iron and myelin, together with brain atrophy, and to clarify their contribution to cognitive and motor disability in MS. Methods In this cross-sectional study, voxel-based morphometry, and voxel-based quantification analyses of R1 and χ maps were conducted in gray matter (GM) and white matter (WM) of 117 MS patients and 53 healthy controls. Voxel-wise between-group differences were assessed with nonparametric permutation tests, while correlations between MRI metrics and clinical variables (global disability, cognitive and motor performance) were assessed both globally and voxel-wise within clusters emerging from the between-group comparisons. Results MS patients showed widespread R1 decrease associated with more limited modifications of χ, with atrophy mainly involving deep GM, posterior and infratentorial regions (p < 0.02). While R1 and χ showed a parallel reduction in several WM tracts (p < 0.001), reduced GM R1 values (p < 0.001) were associated with decreased thalamic χ (p < 0.001) and small clusters of increased χ in the caudate nucleus and prefrontal cortex (p < 0.02). In addition to the atrophy, χ values in the cingulum and corona radiata correlated with global disability and motor performance, while focal demyelination correlated with cognitive performance (p < 0.04). Conclusions We confirmed the presence of widespread R1 changes, involving both GM and WM, and atrophy in MS, with less extensive modifications of tissue χ. While atrophy and χ changes are related to global and motor disability, R1 changes are meaningful correlates of cognition. Key Points • Compared to healthy controls, multiple sclerosis patients showed R1 and χ changes suggestive of iron increase within the basal ganglia and reduced iron and myelin content within (subnuclei of) the thalamus. • Thalamic volume and χ changes significantly predicted clinical disability, as well as pulvinar R1 and χ changes, independently from atrophy. • Atrophy-independent R1 and χ changes, suggestive of thalamic iron and myelin depletion, may represent a sensitive marker of subclinical inflammation.

ObjectiveTo investigate monoaminergic network abnormalities in patients with multiple sclerosis (MS) according to their fatigue and depressive status through a positron emission tomography (PET)-based constrained independent component analysis (ICA) on resting state (RS) functional MRI (fMRI).MethodsIn this prospective study, 213 patients with MS (mean age=40.6±12.5 years; 94/119 men/women; 153 relapsing-remitting; 60 progressive) and 62 healthy controls (HCs, mean age=39.0±10.4 years; 30/32 men/women) underwent neurological, fatigue, depression and RS fMRI assessment. Patterns of dopamine, norepinephrine-related and serotonin-related RS functional connectivity (FC) were derived by ICA, constrained to PET atlases for dopamine, norepinephrine and serotonin transporters, obtained in HCs’ brain.ResultsCompared with HCs, patients with MS showed abnormalities in all three explored monoaminergic networks, mostly with decreased RS FC within PET-guided monoaminergic networks in frontal regions and subcortical areas including the cerebellum and thalamus, and increased RS FC in temporo-parieto-occipital cortical areas, including bilateral precunei.MS-related fatigue was associated with decreased RS FC within the PET-guided dopamine network in the left thalamus and left cerebellum, and with increased RS FC within the PET-guided serotonin network in the left middle occipital gyrus. MS-related depression was associated with more distributed abnormalities involving the three explored monoaminergic networks, resulting in overall reduced RS FC in the frontal lobe, limbic areas and the precuneus.ConclusionsPatients with MS present diffuse dysregulation in the monoaminergic networks. Specific alterations in these networks were associated with fatigue and depression, providing a pathological marker for these bothersome symptoms and putative targets for their treatment.

Objective We aim to evaluate 3-year effects of ocrelizumab (humanized anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS)) on lymphocytes, neutrophils and immunoglobulins: (1) when compared with pre-infusion assessment; (2) over the course of treatment; and (3) possible clinical correlates of the observed immunological modifications. Methods This real-world observational cohort study has been conducted on prospectively collected data from 78 MS patients (mean age 47.8 ± 10.5 years; females 48.7%) commencing on ocrelizumab from 2018, with mean follow-up of 36.5 ± 6.8 months. Clinical data and blood samples were collected every three months. Total lymphocyte count and subpopulations were assessed on peripheral blood using flow cytometry. Serum immunoglobulins were evaluated with nephelometry. Results When compared with pre-infusion values, we observed reduction of total, CD19 and CD20 lymphocyte counts; however, after the first infusion, their levels remained substantially stable. Over time we observed a progressive reduction of CD8 lymphocytes, while no changes were observed for CD4, CD27, CD3CD27, and CD19CD27. After the first infusion, we observed reduction in IgG, which further decreased during the follow-up. Higher probability of EDSS progression was associated with reduced modulation of CD8 lymphocytes. Interpretation Ocrelizumab affects both humoral and cellular immune responses. Disability progression over the follow-up was associated with lower CD8 cytotoxic T-lymphocyte reduction. Changes in humoral response are immediate and sustained, while modulation of cellular immunity occurs progressively through regular re-treatment, and is related to clinical stability.

We aimed to investigate abnormal time-varying functional connectivity (FC) for thalamic sub-regions in multiple sclerosis (MS) and their clinical, cognitive and MRI correlates. Eighty-nine MS patients (49 relapsing-remitting [RR] MS; 40 progressive [P] MS) and 53 matched healthy controls underwent neurological, neuropsychological and resting state fMRI assessment. Time-varying connectivity (TVC) was quantified using sliding-window seed-voxel correlation analysis. Standard deviation of FC across windows was taken as measure of TVC, while mean connectivity across windows expressed static FC. MS patients showed reduced TVC vs controls between most of thalamic sub-regions and fronto-temporo-occipital regions. At the same time, they showed increased static FC between all thalamic sub-regions and structurally connected cortico-subcortical regions. TVC reduction was mainly driven by RRMS; while PMS exhibited a variable pattern of TVC abnormalities, characterized by reduced TVC between frontal/motor thalamic seeds and default-mode network areas and increased TVC vs controls/RRMS between posterior thalamic sub-regions and occipito-temporo-insular cortices, associated with severity of clinical disability. Compared with controls, both cognitively preserved and impaired patients showed reduced TVC between anterior thalamic sub-regions and frontal cortex. Cognitively impaired patients also showed increased TVC of the right postcentral thalamic sub-region with the cingulate cortex and postcentral gyrus vs both controls and cognitively preserved patients. Divergent patterns of TVC thalamic abnormalities were found between RRMS and PMS patients. TVC reduction in RRMS may represent the attempt of thalamic network to keep with stable connections. Conversely, increased TVC of posterior thalamic sub-regions characterized PMS and cognitively impaired MS, possibly reflecting maladaptive mechanisms.

Recent evidence has shown the existence of a CNS ‘waste clearance’ system, defined as the glymphatic system. Glymphatic abnormalities have been described in several neurodegenerative conditions, including Alzheimer’s and Parkinson’s disease. Glymphatic function has not been thoroughly explored in multiple sclerosis, where neurodegenerative processes are intermingled with inflammatory processes. We aimed to investigate glymphatic system function in multiple sclerosis and to evaluate its association with clinical disability, disease course, demyelination and neurodegeneration, quantified using different MRI techniques. In this retrospective study, we enrolled 71 multiple sclerosis patients (49 relapsing-remitting and 22 progressive multiple sclerosis) and 32 age- and sex-matched healthy control subjects. All subjects underwent neurological and MRI assessment including high-resolution T1, T2 and double inversion recovery sequences, diffusion and susceptibility weighted imaging. We calculated the diffusion along perivascular space index, a proxy for glymphatic function, cortical and deep grey matter volume, white and cortical grey matter lesion volume and normal-appearing white matter microstructural damage. Multiple sclerosis patients showed an overall lower diffusion along perivascular space index versus healthy controls (estimated mean difference: −0.09, P = 0.01). Both relapsing-remitting and progressive multiple sclerosis patients had lower diffusion along perivascular space index versus healthy controls (estimated mean difference: −0.06, P = 0.04 for relapsing-remitting and −0.19, P = 0.001 for progressive multiple sclerosis patients). Progressive multiple sclerosis patients showed lower diffusion along perivascular space index versus relapsing-remitting multiple sclerosis patients (estimated mean difference: −0.09, P = 0.03). In multiple sclerosis patients, lower diffusion along perivascular space index was associated with more severe clinical disability (r = −0.45, P = 0.001) and longer disease duration (r = −0.37, P = 0.002). Interestingly, we detected a negative association between diffusion along perivascular space index and disease duration in the first 4.13 years of the disease course (r = −0.38, P = 0.04) without any association thereafter (up to 34 years of disease duration). Lower diffusion along perivascular space index was associated with higher white (r = −0.36, P = 0.003) and cortical (r = −0.41, P = 0.001) lesion volume, more severe cortical (r = 0.30, P = 0.007) and deep (r = 0.42, P = 0.001) grey matter atrophy, reduced fractional anisotropy (r = 0.42, P = 0.001) and increased mean diffusivity (r = −0.45, P = 0.001) in the normal-appearing white matter. Our results suggest that the glymphatic system is impaired in multiple sclerosis, especially in progressive stages. Impaired glymphatic function was associated with measures of both demyelination and neurodegeneration and reflects a more severe clinical disability. These findings suggest that glymphatic impairment may be a pathological mechanism underpinning multiple sclerosis. The dynamic interplay with other pathological substrates of the disease deserves further investigation.

Objective: To report for the first time an Italian epidemiological analysis of the prevalence of multiple sclerosis (MS) in patients with endometriosis (EMS), through the study of the endometriosis population of our referral center; to analyze the clinical profile and perform a laboratory analysis to examine the immune profile and the possible correlation to other autoimmune diseases of the enrolled patients. Methods: We evaluated 1652 women registered with EMS in the University of Naples Federico II and retrospectively searched patients with a co-diagnosis of MS. Clinical features of both conditions were recorded. Serum autoantibody and immune profiles were analyzed. Results: 9 out of 1652 patients presented a co-diagnosis of EMS and MS (9/1652 = 0.005%). Clinically, EMS and MS presented in mild forms. Hashimoto’s thyroiditis was found in two patients (2/9). Even if not statistically significant, a trend of variation in CD4- CD8 T lymphocytes and of B cells were found. Conclusion: Our findings suggest an increased risk of MS in women with EMS. However, large-scale prospective studies are needed.

Background: To date, few cases of multiple sclerosis (MS) patients with concomitant Human Immunodeficiency Virus (HIV) infection have been described. However, none of the previously described cases has been treated with Natalizumab, probably due to the increasing risk of progressive multifocal leukoencephalopathy (PML). Case: We report the case of a patient concomitantly diagnosed for HIV infection and MS treated with combined antiretroviral therapy (cART) and Natalizumab for 19 months, without clinical or radiological MS activity. Conclusions: Our case might suggest considering Natalizumab in patients with concomitant HIV infection, especially for those with significant disease activity requiring a high efficacy disease modifying treatment.

Background and purpose: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. Methods: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. Results: We studied 322 patients (mean age 36.8years, median EDSS score 3, median follow-up 1.94years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p&nbsp

Background Progressive multifocal leukoencephalopathy (PML) can rarely occur in Multiple Sclerosis (MS) patients undergoing dimethyl fumarate (DMF) treatment. Our case stresses the limits of current diagnostic and stratification risk criteria, highlighting the potential role of Magnetic Resonance Imaging (MRI) in advising clinical choices. Case presentation A 54 years old MS male patient treated with DMF, after 3 years of clinical stability developed a subacute clinical worsening. He had no severe lymphopenia but MRI signs suggestive of a coexistence of PML and MS activity. Although his viral title was negative, DMF was discontinued, with clinical and radiological improvement. Conclusions This case highlights the challenges behind PML diagnosis, especially in patients not fulfilling the risk stratification criteria and that might present with concurrent disease activity, stressing the potential role of MRI in informing therapeutic decisions.

Background: Definitions for reliable identification of transition from relapsing-remitting multiple sclerosis (MS) to secondary progressive (SP)MS in clinical cohorts are not available. Objectives: To compare diagnostic performances of two different data-driven SPMS definitions. Methods: Data-driven SPMS definitions based on a version of Lorscheider’s algorithm (DDA) and on the EXPAND trial inclusion criteria were compared, using the neurologist’s definition (ND) as gold standard, in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Akaike information criterion (AIC) and area under the curve (AUC). Results: A cohort of 10,240 MS patients with ⩾5 years of follow-up was extracted from the Italian MS Registry; 880 (8.5%) patients were classified as SPMS according to the neurologist definition, 1806 (17.6%) applying the DDA and 1134 (11.0%) with the EXPAND definition. The DDA showed greater discrimination power (AUC: 0.8 vs 0.6) and a higher sensitivity (77.1% vs 38.0%) than the EXPAND definition, with similar specificity (88.0% vs 91.5%). PPV and NPV were higher using the DDA than considering EXPAND definition (37.5% vs 29.5%; 97.6% vs 94.0%). Conclusion: Data-driven definitions demonstrated greater ability to capture SP transition than neurologist’s definition and the global accuracy of DDA seems to be higher than the EXPAND definition.

This study investigates longitudinal changes in health-related quality of life (HRQoL) in early-onset multiple sclerosis (MS) patients and explores the impact of disease activity (relapses) on such changes. People with MS (PwMS) onset between 12 and 25 years of age were followed longitudinally. At baseline and at year 4, patients were asked to fill the Paediatric Quality of life inventory (PedsQL). Demographic and clinical features were collected at both time points. Longitudinal within-group comparison of HRQoL total score and sub-scores was performed via paired samples t-test. The effect of relapses on the HRQoL changes over time was explored via linear mixed-effects analysis. No longitudinal changes were observed in the overall PedsQL score, nor in the physical, school and psychological functioning. An increase in the social functioning subscale (p < 0.001) and a decrease in the emotional subscale (p = 0.006) were observed. The change in social functioning, but not the one in the emotional subscale, was affected by the occurrence of relapses (p = 0.044). In conclusion, stimulating the patients to accept their emotional responses to health-related limitations, while preserving their social and relational resources seems key to the preservation of an adequate QoL over time in juvenile-onset MS.

Aims We aim to provide real-world evidence on the use of ocrelizumab for treating multiple sclerosis (MS), with specific regard to prescription pattern, adherence, persistence, healthcare resource utilization and related costs, also in relation to other disease-modifying treatments (DMTs). Methods We included 2495 people with MS from the Campania Region (South Italy) who received first or switch DMT prescription from Jan 2018 to Dec 2020, and with at least 6-month follow-up. We collected hospital discharge records, drug prescriptions, and related costs, and calculated persistence (time from first prescription to discontinuation or switch to other DMT), adherence (proportion of days covered (PDC)), annualized hospitalization rate (AHR) for MS-related hospital admissions, and DMT costs. Results Ocrelizumab was the most commonly prescribed DMT (n = 399; age = 45.74 ± 10.98 years; females = 224), after dimethyl fumarate (n = 588) and fingolimod (n = 401); 26% patients treated with ocrelizumab were naïve. When compared with ocrelizumab, the risk of discontinuation was higher for other highly active DMTs (HR = 3.78; p = 0.01), and low/medium efficacy DMTs (HR = 7.59; p p = 0.31), but higher for low/medium efficacy DMTs (Coeff = 0.09; p p = 0.51), and low/medium efficacy DMTs (Coeff = 0.01; p = 0.55). When compared with ocrelizumab, DMT monthly costs were higher for other highly active DMTs (Coeff = 92.30; p p Discussion Ocrelizumab was among the most frequently prescribed DMTs, with 26% prescriptions to treatment-naïve patients, suggesting its relevance in addressing unmet clinical needs (e.g., first approved treatment for primary progressive MS). Ocrelizumab was associated with the highest persistence, confirming its favorable benefit-risk profile. Costs for ocrelizumab were lower than those associated to similarly effective DMTs, in absence of changes in healthcare resource utilization.

Botulinum toxin (BT) is an effective and safe treatment for spasticity, with limited evidence in multiple sclerosis (MS). We aim to describe the use of BT for the management of MS spasticity in the clinical practice, its combination with other anti-spastic treatments in MS and possible MS clinical correlates. This is a multicentre cross-sectional observational study including 386 MS patients, receiving BT for spasticity in 19 Italian centres (age 53.6 ± 10.9 years; female 228 (59.1%); disease duration 18.7 ± 9.2 years; baseline Expanded Disability Status Scale (EDSS) 6.5 (2.0–9.0)). BT was used for improving mobility (n = 170), functioning in activities of daily living (n = 56), pain (n = 56), posturing-hygiene (n = 63) and daily assistance (n = 41). BT formulations were AbobotulinumtoxinA (n = 138), OnabotulinumtoxinA (n = 133) and IncobotulinumtoxinA (n = 115). After conversion to unified dose units, higher BT dose was associated with higher EDSS (Coeff = 0.591; p

Aims: Natalizumab is approved as an infusion every 4 weeks (standard-interval dosing [SID]) in relapsing-remitting multiple sclerosis (MS). Extended-interval dosing (EID) reduces risk of progressive multifocal leukoencephalopathy (PML) compared with SID, but the impact on healthcare resources and costs remains unknown. Methods: In this population-based study, we included 208 natalizumab-treated MS patients who were classified into EID (≤15 infusions in the previous 18 months; n = 51; age = 33.7 ± 11.1 years; female = 72.5%) and SID (>15 infusions in the previous 18 months; n = 157; age = 36.5 ± 10.8 years; female = 68.1%) groups. Results: Natalizumab EID had fewer MS outpatient visits (p = 0.01) and related costs (p = 0.03), and lower natalizumab costs (p

BackgroundWe aim to evaluate whether fertility, pregnancy, delivery and breastfeeding have been actually improving in women with multiple sclerosis (MS), compared with general population, and in relation to treatment features.MethodsWe included 2018–2020 population-level healthcare data on women with MS living in the Campania region (Italy). Fertility, pregnancy and delivery outcomes were obtained from Certificate of Delivery Assistance; breastfeeding was collected up to 6 months after delivery by trained personnel.ResultsOut of 2748 women with MS in childbearing age, 151 women delivered 156 babies. Fertility rate was 0.58 live births per woman with MS, compared with 1.29 in Campania region and 1.25 in Italy. Disease-modifying treatment (DMT) continuation during pregnancy was associated with lower birth weight (coeff −107.09; 95% CI –207.91 to –6.26; p=0.03). Exposure to DMTs with unknown/negative effects on pregnancy was associated with birth defects (OR 8.88; 95% CI 1.35 to 58.41; p=0.02). Birth defects occurred in pregnancies exposed to dimethyl fumarate (2/21 exposed pregnancies), fingolimod (1/11 exposed pregnancies) and natalizumab (2/30 exposed pregnancies). After delivery, 18.8% of women with MS were escalated of DMT efficacy, while 50.7% started on same/similar-efficacy DMTs, and 30.5% did not receive DMT. The probability of breastfeeding was higher in women who were treated with breastfeeding-safe DMTs (OR 5.57; 95% CI 1.09 to 28.55; p=0.03).ConclusionsFertility rate in women with MS remains below the general population. Family planning and subsequent DMT decisions should aim to achieve successful pregnancy, delivery and breastfeeding outcomes, while controlling disease activity.

Despite being a common issue in people with multiple sclerosis (pwMS), sexual dysfunction is still underinvestigated. This work aims to assess the potential determinants of sexual dysfunction in pwMS by considering its relationship with disease severity (in terms of global disability), illness perception, and depressive symptoms. In this multicenter study, 1010 pwMS responded to an online survey. A serial mediation model considering negative illness perception and depressive symptoms as mediators of the relationship between disease severity and sexual dysfunction was conducted using the SPSS PROCESS Macro with bias-corrected bootstrapping (5000 samples). Disease severity exerts an indirect effect on sexual dysfunction via illness perception, both independently and through depressive symptoms. However, the results indicated that illness perception plays a more crucial role in sexual dysfunction in pwMS with mild disability than in pwMS with moderate-severe disability. This study suggests that higher disability increases its magnitude by enhancing negative illness perception, that, in turn, affects sexual dysfunction both directly and through depressive symptoms, especially in pwMS with mild disability. Modulating the effect of illness perception by favoring adaptive coping strategies might represent a valid approach to mitigate sexual dysfunction symptoms in MS.

Objective: We aim to validate an algorithm based on routinely-collected healthcare data to detect incidence of multiple sclerosis (MS) in the Campania Region (South Italy) and to explore its spatial and temporal variations. Methods: We included individuals resident in the Campania Region who had at least one MS record in administrative datasets (drug prescriptions, hospital discharge, outpatients), from 2015 to 2020. We merged administrative to the clinical datasets to ascertain the actual date of diagnosis, and validated the minimum interval from our study baseline (Jan 1, 2015) to first MS records in administrative datasets to detect incident cases. We used Bayesian approach to explore geographical distribution, also including deprivation index as a covariate in the estimation model. We used the capture-recapture method to estimate the proportion of undetected cases. Results: The best performance was achieved by the 12-month interval algorithm, detecting 2,150 incident MS cases, with 74.4% sensitivity (95%CI = 64.1%, 85.9%) and 95.3% specificity (95%CI = 90.7%, 99.8%). The cumulative incidence was 36.68 (95%CI = 35.15, 38.26) per 100,000 from 2016 to 2020. The mean annual incidence was 7.34 (95%CI = 7.03, 7.65) per 100,000 people-year. The geographical distribution of MS relative risk shows a decreasing east-west incidence gradient. The number of expected MS cases was 11% higher than the detected cases. Conclusions: We validated a case-finding algorithm based on administrative data to estimate MS incidence, and its spatial/temporal variations. This algorithm provides up-to-date estimates of MS incidence, and will be used in future studies to evaluate changes in MS incidence in relation to different risk factors.

Pivotal trials showed the effectiveness of the monoclonal antibody ocrelizumab in relapsing and progressive multiple sclerosis (MS). However, data on everyday practice in MS patients and markers of treatment effectiveness are scarce. We aimed to collect real-world data from ocrelizumab-treated MS patients, relapsing-remitting (RR) and progressive MS patients (PMS), including active secondary progressive MS (aSPMS) and primary progressive MS (PPMS) patients, and to explore potential prognostic factors of clinical outcome. Patients were enrolled at MS centres in the Campania region, Italy. We collected clinic-demographic features retrospectively one year before ocrelizumab start (T−1), at ocrelizumab start (T0), and after one year from ocrelizumab start (T1). We explored possible clinical markers of treatment effectiveness in those patients receiving ocrelizumab treatment for at least one year using multilevel-mixed models. We included a total of 383 MS patients (89 RRMS and 294 PMS; 205 females, mean age: 45.8 ± 11.2, disease duration: 12.7 ± 11.6 years). Patients had a mean follow-up of 12.4 ± 8.2 months, and 217 patients completed one-year ocrelizumab treatment. Overall, EDSS increased from T−1 to T0 (coeff. = 0.30, 95% coefficient interval [CI] = 0.19–0.41, p < 0.001) without a further change between T0 and T1 (p = 0.61). RRMS patients did not show an EDSS change between T−1 and T0 nor between T0 and T1. Conversely, PMS patients showed EDSS increase from T−1 to T0 (coeff. = 0.34, 95% CI = 0.22–0.45, p < 0.001) without a further change between T0 and T1 (p = 0.21). PMS patients with a time from conversion shorter than 2 years showed increased EDSS from T−1 to T0 (coeff. = 0.63, 95% CI = 0.18–1.08, p = 0.006) without a further change between T0 and T1 (p = 0.94), whereas PMS patients with a time from conversion longer than 2 years showed increased EDSS from T0 to T1 (coeff. = 0.30, 95% CI = 0.11–0.49, p = 0.002). Naïve patients showed an EDSS decrease between T0 and T1 (coeff. = −0.30, 95% CI = −0.50–−0.09, p = 0.004). In conclusion, our study highlighted that early ocrelizumab treatment is effective in modifying the disability accrual in MS patients.

The current study aimed at exploring the relationship between objective disability, illness perceptions, resilience, fear of COVID-19, and psychological distress (i.e., anxiety, depression, and stress) in people with multiple sclerosis (pwMS) during the second wave of the COVID-19 outbreak. A group of 122 pwMS recruited in an Italian university hospital took part in this cross-sectional monocentric study. Hierarchical multiple linear regression analyses were performed to assess the strength of the hypothesized associations. Results indicated that, differently from cognitive impairment, motor disability was positively associated with anxiety. However, accounting for subjective illness perception, such association was no longer significant. Moreover, accounting for both protective and risk factors in the models, even illness perception was no longer significant, highlighting the central role of resilience and fear of COVID-19 in explaining the negative emotional outcomes. Implications for clinical interventions and psychoeducational trainings are discussed.

Background: Emergency hospital admissions are common in multiple sclerosis (MS), and can highlight unmet medical needs. Objectives: To evaluate burden, predictors and outcomes of MS emergency admissions. Methods: This is a population-based study, conducted in the Campania Region (South Italy) from 2015 to 2019, using hospital discharge records, drug prescriptions and outpatients. The risk of emergency hospital admissions and the likelihood of worse outcomes were evaluated using the Cox regression and multinomial logistic regression models, respectively, in relation to age, sex, disease-modifying treatments (DMTs), comorbidities and adherence. Results: We recorded 1225 emergency admissions for 1001 patients (out of 5765 prevalent MS patients), overall costing 4,143,764.67 EUR. The risk of emergency admissions increased with age (hazard ratio (HR) = 1.02; 95% confidence interval (CI) = 1.01, 1.03; p Conclusion: With 17% people with MS requiring emergency medical care over 5 years, improved management of DMTs and comorbidities could potentially reduce their medical, social and financial burden.

Spinal cord and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) can provide additional information to brain MRI to determine prognosis of multiple sclerosis (MS). However, the real-world impact of routine use of brain MRI with spinal cord and/or Gd sequences is unknown. Our aim was to evaluate the effect of brain, spinal cord and Gd MRI on treatment decisions in MS.In this 2015-2020 population-based study, we performed a retrospective analysis on MS patients resident in the Campania Region (South Italy), with disease modifying treatment (DMT) prescription (n = 6,161). DMTs were classified as platform (dimethyl fumarate, glatiramer acetate, interferon-beta, peg-interferon-beta, teriflunomide), or high-efficacy (alemtuzumab, cladribine, fingolimod, natalizumab, ocrelizumab). We evaluated the association between binary MRI variables and switch from platform to high-efficacy DMT using multivariable logistic regression.The likelihood of switch from platform to high-efficacy DMT was 47% higher when including post-Gd acquisitions to brain and/or spinal cord MRI, 59% higher when including spinal cord acquisitions to brain MRI, and 132% higher when including any MRI compared with no MRI (all p 0.05). The likelihood of switch to high-efficacy DMT decreased over time from treatment start.Our results show that spinal cord and Gd MRI acquisitions can provide relevant information to influence subsequent treatment decisions, especially in early treatment phases, compared with stand-alone brain MRI.

(1) The co-occurrence of AQP4 and myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with demyelinating disorders is extremely rare. In addition, a concomitant involvement of the peripheral nervous system (PNS) has been described either in association with AQP4 antibodies-positive neuromyelitis optica spectrum disorder (NMOSD), or MOG-associated disease. We report on a case of NMOSD with co-occurrence of AQP4 and MOG antibodies and concomitant central and peripheral nervous system involvement. We also reviewed available cases of AQP4-MOG double-positive patients. (2) Brain and spine MRI, cerebrospinal fluid studies, and electrophysiological test were performed. Serum AQP4 and MOG positivity was assessed with live cell-based assay. (3) A 62-year-old woman presented with recurrent optic neuritis, myelitis, and radiculitis, tested positive for AQP4 and MOG antibodies, and was treated successfully with rituximab. (4) Although few cases of AQP4-MOG double-positive patients were already described mostly affecting females with a concomitant spinal cord and optical nerve involvement, we describe the first case of double-positive NMOSD with the peculiar involvement of both central and peripheral nervous system.

Objective: Astrocytes outline the perivascular space (PVS) and regulate fluid exchange through the aquaporin-4 water channel. As neuromyelitis optica is an autoimmune astrocytopathy targeting aquaporin-4, we hypothesized that it could be associatied with PVS abnormalities. Methods: A total of 34 patients, and 46 age- and sex-matched healthy controls from two independent cohorts (exploratory and validation dataset) underwent a standardized 3.0-T magnetic resonance imaging protocol including conventional and diffusion tensor imaging. Susceptibility-weighted imaging was also acquired in the exploratory dataset. We evaluated macroscopic and microstructural abnormalities of PVS in terms of enlargement and water diffusivity (DTI-ALPS index). In the exploration dataset, a susceptibility-weighted sequence was used to draw the regions of interest for the DTI-ALPS index calculation in areas having veins perpendicular to lateral ventricles. Between-group comparisons, correlations, and regression models were run to assess associations between PVS abnormalities, and clinical and magnetic resonance imaging variables. Results: Patients had a higher frequency of severe PVS enlargement in the centrum semiovale (29.4% vs 8.7%), which correlated with brain atrophy, deep grey matter atrophy, and poorer cognitive performance (r-values range: -0.44, -0.36; p values: 0.01-0.046). In both datasets, patients had reduced DTI-ALPS index compared with controls (p values 0.004-0.038). Lower DTI-ALPS index, deep gray matter volume, and cortical volume could discriminate between patients and controls (R2 = 0.62), whereas lower DTI-ALPS index, higher number of myelitis, and higher T2-lesion volume were associated with worse disability (R2 = 0.55). Interpretation: Patients with neuromyelitis optica spectrum disorder are characterized by abnormal enlargement and impaired water diffusion along the PVS, whose clinical implications suggest a direct correlation with disease pathogenesis and severity. ANN NEUROL 2022;92:173-183.