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Background: Therapeutic plasma exchange (TPE) is a highly effective rescue treatment for patients with acute exacerbation of neuroimmunological disease that removes circulating autoantibodies and inflammatory components from the bloodstream. The aims of this study are to explore the safety and the effectiveness of TPE in patients with autoimmune neurological disorders. Methods: We retrospectively evaluated the frequency of adverse events (AEs) and the effectiveness of TPE using the modified Ranking Scale (mRS) in patients with acute neurological flares who underwent TPE at the University Hospital of Palermo. Results: Of 59 patients, the majority underwent TPE due to multiple sclerosis (MS) relapse. In 23.7% of cases, TPE was performed before obtaining a definite diagnosis due to the severity of the clinical presentation. After TPE, the mRS score was globally reduced (p < 0.0001), and this effect was marked in patients with MS, Guillain–Barré syndrome, and myasthenia gravis crisis but not in those with paraneoplastic syndromes. Circulating pathogenetic antibodies, younger age, and the early use of TPE were factors strongly associated with TPE effectiveness. The overall safety profile of TPE was satisfactory with an AE frequency of 15%. Conclusions: These results highlight the early use of TPE in patients with circulating pathogenetic antibodies as well as its favorable safety profile.

Abstract Cerebrospinal fluid (CSF) core biomarkers of Alzheimer’s disease (AD), including amyloid peptide beta-42 (Aβ42), Aβ42/40 ratio, and phosphorylated tau (pTau), are precious tools for supporting AD diagnosis. However, their use in clinical practice is limited due to the invasiveness of CSF collection. Thus, there is intensive research to find alternative, noninvasive, and widely accessible biological matrices to measure AD core biomarkers. In this study, we measured AD core biomarkers in saliva and plasma by a fully automated platform. We enrolled all consecutive patients with cognitive decline. For each patient, we measured Aβ42, Aβ40, and pTau levels in CSF, saliva, and plasma by Lumipulse G1200 (Fujirebio). We included forty-two patients, of whom 27 had AD. Levels of all biomarkers significantly differed in the three biofluids, with saliva having the lowest and CSF the highest levels of Aβ42, Aβ40, and pTau. A positive correlation of pTau, Aβ42/40 ratio, and pTau/Aβ42 ratio levels in CSF and plasma was detected, while no correlation between any biomarker in CSF and saliva was found. Our findings suggest that plasma but not saliva could represent a surrogate biofluid for measuring core AD biomarkers. Specifically, plasma Aβ42/40 ratio, pTau/Aβ42 ratio, and pTau could serve as surrogates of the corresponding CSF biomarkers.

Abstract Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease due to an autoimmune chronic inflammatory response, yet the etiology is currently not completely understood. It is already known that physical activity plays an essential role in improving quality of life, especially in neuropathological conditions. The study was aimed to investigate the possible benefits of high-intensity interval training (HIIT) in bone and lipid metabolism markers, and neuromotor abilities in MS patients. 130 participants were recruited; 16 subjects with MS met the inclusion criteria and were included in the data analysis. The patients were randomly assigned to two groups: a Control group (CG) (34.88 ± 4.45 yrs) that didn’t perform any physical activity and the Exercise group (EG) (36.20 ± 7.80 yrs) that performed HIIT protocol. The training program was conducted remotely by a kinesiologist. It was performed three times a week for 8 weeks. At the beginning (T0) and the end of the study (T1) physical function tests, bone remodelling markers, and lipid markers analyses were performed. After 8 weeks of training the wall squat (s) (T0 = 27.18 ± 4.21; T1 = 41.68 ± 5.38, p ≤ 0.01) and Time Up and Go test (s) (T0 = 7.65 ± 0.43; T1 = 6.34 ± 0.38 p ≤ 0.01) performances improved; lipid markers analysis showed a decrease in Total (mg/dl) (T0 = 187.22 ± 15.73; T1 = 173.44 ± 13.03, p ≤ 0.05) and LDL (mg/dl) (T0 = 108 ± 21.08; T1 = 95.02 ± 17.99, p

Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 ​at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b. Confirmed Expanded Disability Status Scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. Out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 ​± ​25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 ​± ​19.8 years) were enrolled. After applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. The proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p ​= ​0.01). The proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p ​= ​0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67–5.7; p ​= ​0.006 and HR 2.04, 25%CI 1.22–3.35; p ​= ​0.01, respectively). Patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04–4.87; p ​= ​0.001). Treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months.

Abstract Objective Vaccines are a major achievement of science, and new vaccines against SARS‐CoV‐2 are protecting the entire population from a life‐threatening infection. Although several neurological complications or worsening of pre‐existing neurological conditions after vaccination have been observed, whether a biological plausibility exist between new vaccines against‐SARS‐CoV‐2 and neurological consequences is unclear. The aim of this study is to evaluate whether vaccines against SARS‐CoV‐2 induce systemic or cerebrospinal fluid alterations in patients with neurological disorders. Methods Patients who underwent lumbar puncture (LP) between February 2021 and October 2022 were enrolled. Serum C‐reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), cerebrospinal fluid total protein content (CSF‐TPc), glucose CSF/serum ratio, number of CSF cells per cubic millimeter, and CSF neurofilament light chain (CSF‐NfL) were compared between unvaccinated and vaccinated patients. Results A total of 110 patients were included and fitted into three groups according firstly to vaccination status (vaccinated and unvaccinated) and then to time from last dose of vaccine to LP (within or after 3 months). TPc, CSF/SGlu ratio, number of cells per cubic millimeter, CSF‐NfL, CRP, and NLR were not different between groups (all p > 0.05), and also, they did not differ neither according to age nor diagnosis. No relevant differences between groups were also noticed when the at‐risk time window was set to 6 weeks. Interpretation No signs of neuroinflammation, axonal loss and systemic inflammation were found in patients with neurological disorders after anti‐SARS‐CoV‐2 vaccination compared with unvaccinated ones.

Abstract Aims Neuroinflammation might be involved in the degeneration and progression of Amyotrophic Lateral Sclerosis (ALS). Here, we studied the role of the circulating lymphocytes in ALS, in particular the NK cells. We focused on the relationship between blood lymphocytes, ALS clinical subtype and disease severity. Subjects and Methods Blood samples were collected from 92 patients with sporadic ALS, 21 patients with Primary Lateral Sclerosis (PLS) and 37 patients affected by primary progressive multiple sclerosis (PPMS) with inactive plaques. Blood was taken from ALS and controls at the time of diagnosis/referral. Circulating lymphocytes were analyzed by flow cytometry with specific antibodies. Values were expressed as absolute number (n°/µl) of viable lymphocytes subpopulations in ALS were compared with controls. Multivariable analysis was made using site of onset, gender changes in ALSFRS-R and disease progression rate (calculated as ΔFS score). Results Age at onset was 65y (58–71) in ALS (spinal 67.4%; bulbar, 32.6%), 57y (48–78) in PLS and 56y (44–68) PPMS. Absolute blood levels of the lymphocytes in the different cohorts were within normal range. Furthermore, while levels of lymphocytes T and B were not different between disease groups, NK cells were increased in the ALS cohort (ALS = 236 [158–360] vs. Controls = 174[113–240], p

AimsDuring pregnancy, fetal cells can migrate to the mother via blood circulation. A percentage of these cells survive in maternal tissues for decades generating a population of fetal microchimeric cells (fMCs), whose biological role is unclear. The aim of this study was to investigate the association between the sex of offspring, an indirect marker of fMCs, and magnetic resonance imaging (MRI) features in women with multiple sclerosis (MS).MethodsWe recruited 26 nulliparous MS patients (NPp), 20 patients with at least one male son (XYp), and 8 patients with only daughters (XXp). Each patient underwent brain MR scan to acquire 3D-T2w FLAIR FatSat and 3D-T1w FSPGR/TFE. Lesion Segmentation Tool (LST) and FreeSurfer were used to obtain quantitative data from MRI. Additional data were collected using medical records. Multiple regression models were applied to evaluate the association between sex of offspring and MS data.ResultsComparing NPp and XXp, we found that NPp had larger 4th ventricle volume (2.02 ± 0.59 vs. 1.70 ± 0.41; p = 0.022), smaller left entorhinal volume (0.55 ± 0.17 vs. 0.68 ± 0.25; p = 0.028), and lower thickness in the following cortical areas: left paracentral (2.34 ± 0.16 vs. 2.39 ± 0.17; p = 0.043), left precuneus (2.27 ± 0.11 vs. 2.34 ± 0.16; p = 0.046), right lateral occipital (2.14 ± 0.11 vs. 2.25 ± 0.08; p = 0.006). NPp also had lower thickness in left paracentral cortex (2.34 ± 0.16 vs. 2.46 ± 0.17; p = 0.004), left precalcarine cortex (1.64 ± 0.14 vs. 1.72 ± 0.12; p = 0.041), and right paracentral cortex (2.34 ± 0.17 vs. 2.42 ± 0.14; p = 0.015) when compared to XYp. Comparing XYp and XXp, we found that XYp had higher thickness in left cuneus (1.80 ± 0.14 vs. 1.93 ± 0.10; p = 0.042) and left pericalcarine areas (1.59 ± 0.19 vs. 1.72 ± 0.12; p = 0.032) and lower thickness in right lateral occipital cortex (2.25 ± 0.08 vs. 2.18 ± 0.13; p = 0.027).DiscussionOur findings suggested an association between the sex of offspring and brain atrophy. Considering the sex of offspring as an indirect marker of fMCs, we speculated that fMCs could accumulate in different brain areas modulating MS neuropathological processes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with several neurological disorders including headache, facial palsy, encephalitis, stroke, demyelinating disorders. The present report will discuss cases of multiple sclerosis (MS) onset and relapse both beginning early after SARS-CoV-2 infection. In both cases, magnetic resonance imaging (MRI) showed widespread bilateral subcortical and periventricular active lesions. Serum IgG against SARS-CoV-2 Spike antigens confirmed seroconversion with titers that are considered not definitely protective against possible reinfection. We hypothesize that SARS-CoV-2 infection, as previously reported for other viruses, could drive an active inflammatory response that can contribute either to the onset of MS or its relapse. The presented data further support the importance of vaccination in individuals with MS.

The growing incidence of neurodegenerative disorders in our populations is leading the research to identify potential biomarkers and targets for facilitating their early management and treatments. Biomarkers represent the crucial indicators of both physiological and pathological processes. Specific changes in molecular and cellular mechanisms of physiological processes result in biochemical alterations at systemic level, which can give us comprehensive information regarding the nature of any disease. In addition, any disease biomarker should be specific and reliable, able to consent of distinguishing the physiological condition of a tissue, organ, or system from disease, and be diverse among the various diseases, or subgroups or phenotypes of them. Accordingly, biomarkers can predict chances for diseases, facilitate their early diagnosis, and set guidelines for the development of new therapies for treating diseases and disease-making process. Here, we focus our attention on brain neurotrophic factor (BDNF)–tropomyosin receptor kinase (Trk) pathway, describing its multiple roles in the maintenance of central nervous system (CNS) health, as well as its implication in the pathogenesis of multiple sclerosis (MS). In addition, we also evidence the features of such pathway, which make of it a potential MS biomarker and therapeutic target.

Multiple sclerosis (MS) is an autoimmune and degenerative disorder of the central nervous system (CNS) that causes a progressive loss of motor and cognitive performances. Moreover, since the earlier phases, axonal loss as well as neuronal degeneration and a failure of oligodendrocytes to promote myelin repair have been demonstrated. In previous studies, it has been shown that the treatment of rat neuronal primary cultures with serum from MS patients can be toxic for neurons. Here we report a pilot investigation showing that CSF from patients contains extracellular vesicles (EVs) able to induce cell death in rat cultured astrocytes. Although these data are still preliminary, they suggest at least two notable considerations: i) EVs can be instrumental to pathology, and their concentration in CSF might be proportional to MS severity; ii) astrocytes can be part of the degenerative process. As a consequence, we propose that cultured astrocytes can be used as a model to study the toxicity of EVs from patients affected by MS at different stages. In addition, we suggest that EVs and their cargoes might be used as biomarkers of MS severity.

Background and aims: No consensus exists on how aggressively to treat relapsing–remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC). Methods: RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups. Results: The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5–11.7) years. Mean annual delta-EDSS values were all significantly ( p

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by John Cunningham Virus (JCV). We report four PML cases in immunocompromised patients, respectively treated with (1) Natalizumab, (2) Rituximab, (3) autologous stem-cell transplantation, and (4) Tacrolimus. All patients underwent neurological examination, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), JCV-DNA research on biological samples, and lymphocytes subpopulation study. All cases presented with motor, behavioural, and cognitive disorders. Visual, sensitive, and cerebellar deficits developed in three cases. MRI revealed widespread progressive demyelinating areas with active borders; three patients presented contrast enhancement. One patient developed inflammatory reconstitution syndrome (IRIS). At MRS, all cases presented decreased N-acetyl-aspartate (NAA) and three cases showed increased choline (Cho). In one patient, plasma and urine tested positive for JCV-DNA, while cerebrospinal fluid (CSF) analysis confirmed JCV in two patients. The fourth patient had a low JCV-DNA blood titer and brain biopsy showed subacute necrosis. Two patients had abnormal lymphocyte subpopulations. Three patients underwent therapy with Mirtazapine, one of whom received Mefloquine in add-on. No clinical response was registered. Clinical onset, MRI and MRS were highly suggestive of PML in all patients, despite three cases presented contrast enhancement. In three cases JCV-DNA detection in biological samples confirmed the diagnosis. The fourth patient fulfilled diagnosis of “presumptive PML”. Our data confirm the importance to complete the diagnostic workup despite the presence of findings not completely consistent with classical PML. We hypothesize that atypical characteristics could due to the clinical conditions leading to PML.

Multiple factors combined are currently recognized as contributors to cognitive decline. The main independent risk factor for cognitive impairment and dementia is advanced age followed by other determinants such as genetic, socioeconomic, and environmental factors, including nutrition and physical activity. In the next decades, a rise in dementia cases is expected due largely to the aging of the world population. There are no hitherto effective pharmaceutical therapies to treat age-associated cognitive impairment and dementia, which underscores the crucial role of prevention. A relationship among diet, physical activity, and other lifestyle factors with cognitive function has been intensively studied with mounting evidence supporting the role of these determinants in the development of cognitive decline and dementia, which is a chief cause of disability globally. Several dietary patterns, foods, and nutrients have been investigated in this regard, with some encouraging and other disappointing results. This review presents the current evidence for the effects of dietary patterns, dietary components, some supplements, physical activity, sleep patterns, and social engagement on the prevention or delay of the onset of age-related cognitive decline and dementia.

Physical activity could play a key role in improving the quality of life, particularly in patients with nervous system diseases such as multiple sclerosis (MS). Through lactacid anaerobic training, this study aims to investigate the effects at a bio-psycho-physical level to counteract the chronic fatigue associated with the pathology, and to improve mental health at a psychological and neurotrophic level. Eight subjects (age: 34.88 ± 4.45 years) affected by multiple sclerosis were involved. A lactate threshold training program was administered biweekly for 12 weeks at the beginning of the study (T0), at the end of the study (T1) and at 9 months after the end of the study (T2), with physical, psychological and hematochemicals parameters, and dietary habits being tested. The results obtained confirmed that lactacid exercise can influence brain-derived neurotrophic factor (BDNF) levels as well as dehydroepiandrosterone sulfate (DHEAS) levels. In addition, levels of baseline lactate, which could be best used as an energy substrate, showed a decrease after the protocol training. Self-efficacy regarding worries and concerns management significantly increased from T0 to T1. The eating attitudes test (EAT-26) did not highlight any eating disease in the patients with a normal diet enrolled in our study. Physical exercise also greatly influenced the patients psychologically and emotionally, increasing their self-esteem. Lactate threshold training, together with dietary habits, appears to exert synergic positive effects on inflammation, neural plasticity and neuroprotection, producing preventive effects on MS symptoms and progression.

Studies on the role of nutritional factors and physical activity (PA) in the pathogenesis of multiple sclerosis (MS) go back a long time. Despite the intrinsic difficulty of studying their positive or negative role in MS, the interest of researchers on these topics increased during the last few decades, since the role of diet has been investigated with the perspective of the association with disease-modifying drugs (DMD). The association of DMD, diets, and PA might have an additive effect in modifying disease severity. Among the various diets investigated (low-carbohydrate, gluten-free, Mediterranean, low-fat, fasting-mimicking, and Western diets) only low-carbohydrate, Mediterranean, and fast-mimicking diets have shown both in animal models and in humans a positive effect on MS course and in patient-reported outcomes (PROs). However, the Mediterranean diet is easier to be maintained compared to fast-mimicking and low-carbohydrate diets, which may lead to detrimental side effects requiring careful clinical monitoring. Conversely, the Western diet, which is characterized by a high intake of highly saturated fats and carbohydrates, may lead to the activation of pro-inflammatory immune pathways and is therefore not recommended. PA showed a positive effect both in animal models as well as on disease course and PROs in humans. Training with combined exercises is considered the more effective approach.

Abstract Background The association between multiple sclerosis (MS) and cancer has long been investigated with conflicting results. Several reports suggest an increased cancer risk among MS patients treated with immunosuppressant (IS) drugs. Methods We performed a cohort study including MS patients recruited at the Neurological Department of the University of Palermo. Mean follow-up period was ten years for the whole cohort. We calculated cancer incidence among patients treated with IS. Incidence rates were compared in the cohort by calculating the relative risk according to length and dose of exposure to IS. Cancer incidence among MS patients was compared to cancer incidence in the general population of Sicily in similar age groups. Results On an overall cohort of 531 MS patients (346 women and 185 men) exposed to IS, we estimated a crude incidence rate for cancer of 2.26% (2.02% in women, 2.7% in men). Cancer risk was higher compared to rates observed among an equal number of patients not exposed to IS, and to the risk in the general population in Sicily at similar age groups (adjusted HR: 11.05; CI 1.67–73.3; p = 0.013). Conclusion The present study showed a higher cancer risk in MS patients associated only to previous IS exposure. Studies on long-term outcomes are essential to evaluate the possibility that treatment options that need to be considered for a long time-period may modify risk for life threatening diseases.

Migraine is a highly disabling disease characterized by recurrent pain. Despite an intensive effort, mechanisms of migraine pathophysiology still represent an unsolved issue. Evidence from both animal and human studies suggests that migraine is characterized by hyperresponsivity or hyperexcitability of sensory cortices, especially the visual cortex. This phenomenon, in turn, may affect multisensory processing. Indeed, migraineurs present with an abnormal, reduced, perception of the Sound-induced Flash Illusion (SiFI), a crossmodal illusion that relies on optimal integration of visual and auditory stimuli by the occipital visual cortex. Decreasing visual cortical excitability with transcranial direct current stimulation (tDCS) can increase the SiFI in healthy subjects. Moving away from these issues, we applied cathodal tDCS over the visual cortex of migraineurs, with and without aura, in order to decrease cortical excitability and thus physiologically restoring the perception of a reliable SiFI. Differently from our expectations, tDCS was unable to reliably modulate SiFI in migraine. The chronic, relatively excessive, visual cortex hyperexcitability, featuring the migraineur brain, may render tDCS ineffective for restoring multisensory processing in this disease.

Background: Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D3. The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D3, and MS risk. Methods: We analyzed two polymorphisms in the FOXP3 gene (rs3761547 and rs3761548) and a polymorphism in the GATA3 gene (rs3824662) in 106 MS patients and 113 healthy controls. Serum 25(OH)D3 was also measured in all participants. Results: No statistically significant genotypic and allelic differences were found in the distribution of FOXP3 rs3761547 and rs3761548, or GATA3 rs3824662 in the MS patients, compared with controls. Patients that were homozygous for rs3761547 had lower 25(OH)D3 levels. Conclusions: Our findings did not show any association among FOXP3 and GATA3 SNPs, vitamin D3, and MS susceptibility.

This study was designed based on the hypothesis that changes in both the levels and surface marker expression of extracellular vesicles (EVs) isolated from the cerebrospinal fluid (CSF) may be associated with the clinical form, disease activity, and severity of multiple sclerosis (MS). The analyzes were performed on subjects affected by MS or other neurological disorders. EVs, which were isolated by ultracentrifugation of CSF samples, were characterized by flow cytometry. A panel of fluorescent antibodies was used to identify the EV origin: CD4, CCR3, CCR5, CD19, and CD200, as well as isolectin IB4. The Mann–Whitney U-test and Kruskal–Wallis test were used for statistical analyzes. EVs isolated from the CSF were more abundant in patients with progressive MS and in those with a clinically isolated syndrome than in all the other groups examined. Furthermore, an important change in the number of EVs and in their surface marker expression occurred during active phases of MS [i.e., clinical relapses and the presence of enhancing lesions on magnetic resonance imaging (MRI)]. In particular, the number of CSF-EVs increased in patients affected by MS during clinical relapse; this finding was associated with a decrease in the number of CD19+/CD200+ (naïve B cells) EVs. These markers are expressed by immature and naïve B lymphocytes, and to the best of our knowledge, this double staining has never been associated with MS, but their reduction has been observed in patients with another type of Th1 cell-mediated autoimmune disease. In contrast, the presence of lesions in the brain and spine on gadolinium-enhanced MRI was associated with an increase in the numbers of CCR3+/CCR5+ (subset of CD8 memory T cells), CD4+/CCR3+ (Th2 cells), and CD4+/CCR5+ (Th1 cells) CSF-EVs. Two points are worth emphasizing: (i) the data obtained in this study confirm that CSF-EVs represent a potentially promising tool to identify biomarkers specific for different phases of MS; and (ii) Considering the role of EVs in intercellular communication, our results provide some insights that improve our understanding of the relationships among some of the cell types that are mainly involved in MS pathogenesis (e.g., lymphocytes, glia, and neurons).

Background: The aim of the study was to evaluate the achievement of ‘no evidence of disease activity’ (NEDA) over a 12-month period in a large multicenter population with relapsing remitting multiple sclerosis (RRMS) treated with delayed-release dimethyl fumarate (DMF) and teriflunomide (TRF) using a propensity-score adjustment. Methods: A time-to-event method was used to determine the percentages of patients with RRMS (pwRRMS) in both groups achieving NEDA 3 (no relapses, no 12-week confirmed disability progression, and no new T2/gadolinium-enhancing brain lesions). We described the safety profile of the investigated drugs. Results: Of the 587 pwRRMS treated with DMF and the 316 pwRRMS treated with TRF, 468 pwRRMS were successfully paired by propensity score: 234 on DMF and 234 on TRF. The percentages of pwRRMS who achieved NEDA 3 were 80.3% in the DMF group and 77.2% in the TRF group. Serious adverse events occurred in four (1.9%) pwRRMS on DMF and in three (1.3%) pwRRMS on TRF. Conclusions: DMF and TRF significantly impacted RRMS disease activity in our study. Serious safety concerns were recorded in less than 2% of the studied population.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. At present, the molecular mechanisms causing the initiation, development and progression of MS are poorly understood, and no reliable proteinaceous disease markers are available. In this study, we used an immunoproteomics approach to identify autoreactive antibodies in the cerebrospinal fluid of MS patients to use as candidate markers with potential diagnostic value. We identified an autoreactive anti-transferrin antibody that may have a potential link with the development and progression of MS. We found this antibody at high levels also in the serum of MS patients and created an immunoenzymatic assay to detect it. Because of the complexity and heterogeneity of multiple sclerosis, it is difficult to find a single marker for all of the processes involved in the origin and progression of the disease, so the development of a panel of biomarkers is desirable, and anti-transferrin antibody could be one of these.

Marburg's disease (MD) is an extremely rare and aggressive form of multiple sclerosis (MS). In some cases, MD presents with tumefactive demyelinating lesions with a “tumor-like” appearance in MRI images, for which it may be difficult to achieve a form of differential diagnosis between definitive tumors or abscesses. Here we report a case of MD histopathologically confirmed after neuronavigationguided biopsy. Postoperative course was uneventful and following discharge, the patient attended outpatient follow-up appointments and received i.v. cyclophopsphamide, achieving progressive clinical remission. A nine-month follow-up brain MRI scan with gadolinium showed no signs of progressing demyelinating disease with an evident reduction of the biopsied lesion, and almost complete retrogression of the other two lesions. In our opinion, and through the analysis of currently available literature, early neuronavigation-guided biopsy is a highly recommend, valuable, and safe diagnostic tool; it is also preferable to stereotactic biopsy, since its benefits include a very low bleeding rate and brain damage risk, with minimum mortality and morbidity rates. It also allows the identification of the specific histological pattern, helping to select the best medical treatment approach and contributing to increase patient outcome and life expectancy.