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Background:There is emerging evidence that intrathecal IgM synthesis (ITMS) is a risk factor for conversion to clinically defined multiple sclerosis (CDMS) in clinically isolated syndrome (CIS) patients.Objectives:The objective of this study is to verify the prognostic role of ITMS as a risk factor for the second clinical attack in patients after the first demyelinating event.Methods:Monocentric observational study performed on prospectively acquired clinical data and retrospective evaluation of magnetic resonance imaging (MRI) data. ITMS was assessed according to Reiber’s non-linear function. We compared time to the second attack by using Kaplan–Meier curves and performed adjustment by Cox regression analysis.Results:Demographics and clinical data were collected prospectively in a cohort of 68 patients. ITMS occurred in 40% (27/68) of patients who had a higher T1-hypointense lesion load at brain MRI ( p = 0.041). In multivariate Cox regression analysis (adjusted for age, sex, baseline Expanded Disability Status Scale, IgG oligoclonal bands and disease-modifying treatment exposure), relapsing-remitting multiple sclerosis (MS) patients with ITMS were at higher risk to experience a second clinical attack (adjusted hazard ratio (aHR) = 6.3, 95% confidence interval (CI) = 2.1–18.4, p = 0.001).Conclusion:Together with previous studies, our findings support the role of ITMS as a prognostic biomarker in MS.

Background The spectrum of differential diagnosis of acquired demyelinating disorders of the central nervous system has been recently broadened. There is now growing evidence that supports anti-myelin oligodendrocyte antibodies associated demyelination as a distinct disease entity, with some clinical characteristics that somehow overlap those of Multiple Sclerosis (MS) and anti-AQP4+ Neuromyelitis Optica Spectrum Disorders (AQP4+NMOSD) but different pathogenesis and treatment strategies. Summary We hereby present 3 cases of anti-MOG+ patients with different disease courses - ranging from mild to severe - all presenting with Optic neuritis (ON) at the onset. Optic neuritis (ON) is a common manifestation of different central nervous system (CNS) inflammatory disorders and can represent the first clinical event of MS and NMOSD. ON is also the most common presentation of antiMOG demyelinating disorders, followed by - and sometimes associated with - myelitis, most commonly extended over more than 2 spinal cord segments and defined as longitudinally extended transverse myelitis (LETM). All the three patients tested negative for oligoclonal bands in CSF and anti-AQP4 Ab in serum, had a relapsing disease course characterized by prominent involvement of the optic nerve and spinal cord, with good recovery after treatment with high-dose corticosteroids. However, they had a different disease course at follow-up and underwent different treatment approaches. Conclusions Since anti-MOG+ patients can have a multiphasic disease course and accumulate disability over time, a high degree of suspicion and early diagnosis are of critical importance for treatment decision-making in clinical practice. Aim The aim of this case report is to enhance focus on an emerging disease spectrum among acquired CNS demyelinating disorders.

There is limited information on socio-professional attainment in pediatric-onset multiple sclerosis (POMS) compared with adult-onset MS (AOMS).To assess socio-professional outcomes in POMS and AOMS and variables influencing these outcomes.One-hundred-fifteen AOMS and 111 POMS patients underwent neuropsychological testing (Brief Repeatable Battery, Stroop test), assessment of cognitive reserve (CR) (education, National Adult reading Test -NART, Barratt Simplified Measure of Social Status), fatigue (Fatigue Severity Scale), depression (Montgomery-Åsberg Depression Rating Scale), socio-professional performance (Work and Social Adjustment Scale -WSAS). Prognostic factors were assessed using logistic and linear multivariable regression analyses.34.5% of patients showed CI without significant differences between AOMS and POMS. Cognitively impaired patients were older (p=0.024), had higher EDSS scores (p=0.041) and lower IQ (p0.001) compared with cognitively preserved patients. Better WSAS scores were associated with younger age (p=0.007), lower EDSS (p0.001) and higher educational levels (p=0.001). Fourteen POMS (13%) and six AOMS (5%) achieved a lower educational level compared with their parents (p=0.06). POMS exhibiting a lower than expected educational level, had a lower median IQ compared with the remaining subjects (101 vs 106.5; p=0.03). Unemployment rate was predicted by higher disability (p=0.044) and lower educational levels (p0.001). Occupational complexity was positively correlated to educational level (0.001) and NART scores (0.040).This study underscores the complex relationships between cognition and educational, socioeconomic and professional attainment in MS and supports a protective role of CR in both POMS and AOMS.

An ever-expanding number of disease-modifying drugs for multiple sclerosis have become available in recent years, after demonstrating efficacy in clinical trials. In the real-world setting, however, disease-modifying drugs are prescribed in patient populations that differ from those included in pivotal studies, where extreme age patients are usually excluded or under-represented. In this multicentre, observational, retrospective Italian cohort study, we evaluated treatment exposure in three cohorts of patients with relapsing-remitting multiple sclerosis defined by age at onset: paediatric-onset (≤18 years), adult-onset (18–49 years) and late-onset multiple sclerosis (≥50 years). We included patients with a relapsing-remitting phenotype, ≥5 years follow-up, ≥3 Expanded Disability Status Scale (EDSS) evaluations and a first neurological evaluation within 3 years from the first demyelinating event. Multivariate Cox regression models (adjusted hazard ratio with 95% confidence intervals) were used to assess the risk of reaching a first 12-month confirmed disability worsening and the risk of reaching a sustained EDSS of 4.0. The effect of disease-modifying drugs was assessed as quartiles of time exposure. We found that disease-modifying drugs reduced the risk of 12-month confirmed disability worsening, with a progressive risk reduction in different quartiles of exposure in paediatric-onset and adult-onset patients [adjusted hazard ratios in non-exposed versus exposed >62% of the follow-up time: 8.0 (3.5–17.9) for paediatric-onset and 6.3 (4.9–8.0) for adult-onset, P

We reported the case of a John Cunningham virus (JCV) and human herpesvirus 6 (HHV-6) mediated progressive multifocal leukoencephalopathy (PML) after human stem cell transplant, reactivated 6 months later in absence of immunosuppressive therapy, successfully treated with anti-5HT2A receptors agents and antiviral therapy. Few cases of JCV and HHV-6 coinfection associated PML are described in literature and the role of HHV-6 in the pathogenesis and prognosis of PML is not completely clear. Our case suggests that, in a possible PML, the research of HHV-6 and JCV should be always performed on cerebrospinal fluid (CSF) and on blood samples and in case of detection of HHV-6 DNA a chromosomally integrated human herpesvirus 6(ciHHV-6) should be excluded. Furthermore we recommend to start an appropriate therapy with antiviral and anti-5HT2A receptors agents in case of possible PML due to JCV and HHV-6 coinfection.

Background Many potentially modifiable risk factors for MS are investigated. It is not known, however, if these factors also apply to MS-related cognitive impairment (CI), a frequent consequence of MS. Objective The aim of our study was to assess risk factors for CI in MS patients, focusing on environmental exposures, lifestyle and comorbidities. Methods We included MS patients referring to MS Centers in Florence and Barletta between 2014 and 2017. Neuropsychological performance was assessed through the Rao’s battery and Stroop test, cognitive reserve (premorbid intelligence quotient–IQ) was evaluated using the National Adult Reading Test (NART). Potential risk factors were investigated through a semi-structured questionnaire. Results 150 patients were included. CI was detected in 45 (30%) subjects and was associated with older age (p