Trans-synaptic degeneration in the optic pathway. A study in clinically isolated syndrome and early relapsing-remitting multiple sclerosis with or without optic neuritis

Increasing evidence suggest that neuronal damage is an early and diffuse feature of Multiple Sclerosis (MS) pathology. Analysis of the optic pathway may help to clarify the mechanisms involved in grey matter damage in MS. Purpose of our study was to investigate the relationship between inflammation and neurodegeneration and to achieve evidence of trans-synaptic degeneration in the optic pathway in MS at clinical onset

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Alemtuzumab following natalizumab in highly active paediatric-onset multiple sclerosis

We evaluated the occurrence of infusion-associated reactions, severe adverse events and no evidence of disease activity 3 status of a therapeutic course consisting of natalizumab followed by alemtuzumab in paediatric-onset multiple sclerosis. Five paediatric-onset multiple sclerosis (age range 16-17 years) were followed for a median of 3.9 years (interquartile range 3.1-5.0). At a natalizumab break (mean infusions 25.6\u2009\ub1\u20091.3) patients were switched to alemtuzumab and completed the two therapy courses. Few mild/moderate infusion-associated reactions were observed during alemtuzumab infusion. No severe adverse events were detected. Natalizumab followed by alemtuzumab proved to be a well-tolerated therapeutic course in paediatric-onset multiple sclerosis. Moreover, paediatric-onset multiple sclerosis maintained the no evidence of disease activity 3 status throughout the follow-up

Multiple Sclerosis-Related “Spasticity-Plus Syndrome” May Benefit from Early Nabiximols Treatment

We present the case of a 42-year-old woman affected by relapsing-remitting multiple sclerosis who presented an extensive involvement of the spinal cord during the disease course. After a trial on first-line treatment, which she discontinued due to poor compliance, she was switched to intravenous ocrelizumab 600 mg every 6 months. At 10 years from the disease onset, as a result of the extensive spinal cord involvement, she began to complain of progressive and rapid reduction in ambulatory performance due to spasticity of the right leg, instability and severe fatigability, together with overactive bladder symptoms. The early introduction of nabiximols positively impacted on the patient’s symptoms and on the neurological examination, as well as on her quality of life

Retinal inner nuclear layer thinning is decreased and associates with the clinical outcome in ocrelizumab-treated primary progressive multiple sclerosis

Background Ocrelizumab was found to decrease brain atrophy rate in primary progressive multiple sclerosis (PPMS), but no data are currently available on the effect of ocrelizumab on retinal layer thicknesses in the PPMS population. Objective To assess retinal layer changes in ocrelizumab-treated PPMS and test their possible application as biomarkers of therapy response. Methods 36 PPMS patients, treated with ocrelizumab for at least 6 months, and 39 sex- and age-matched healthy controls (HC) were included in a blind, longitudinal study. Spectrum-domain optical coherence tomography (SD-OCT) was performed at study entry (T0) and after 6 (T6) and 12 months (T12). At month 24 (T24), patients were divided into responders (no evidence of 1-year confirmed disability progression, 1y-CDP) and non-responders (evidence of 1y-CDP). Results At T24, 23/36 (64%) patients were considered responders and 13/36 (36%) non-responders. At T0, peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) and inner retinal layer (IRL) volume were significantly lower in PPMS compared to HC (p = 0.001 for all comparisons). At T6 and T12, non-responders significantly differed in the inner nuclear layer (INL) thinning rate compared to responders (p = 0.005 at both time-points). Conclusions Ocrelizumab significantly slows down INL thinning rate in PPMS responders. The longitudinal analysis of retina layer changes by means of OCT may be a promising prognostic test, and merits further investigations

Hyper-Reflecting Foci in Multiple Sclerosis Retina Associate With Macrophage/Microglia-Derived Cytokines in Cerebrospinal Fluid

BackgroundIncreasing evidence suggests that retinal hyper-reflecting foci (HRF) might be clusters of activated and proliferating microglia. Since microglia are widespread activated in multiple sclerosis (MS) brain, its evaluation in retina may help to understand and monitor MS-related pathology. AimThis study aims at investigating the association of HRF with cerebrospinal fluid (CSF) cytokines and MRI parameters in relapsing-remitting MS (RRMS). MethodsNineteen RRMS at clinical onset and 15 non-inflammatory neurological disorders (NIND) underwent brain 3T MRI and CSF examination. Optical coherence tomography (OCT) analysis, including HRF count, was performed on RRMS patients. Sixty-nine cytokines/chemokines were analyzed in the CSF by multiplex technology. ResultsIn RRMS, HRF count in the ganglion cell layer (GCL) was associated with IL-1Ra, IL-9, IL-15, IFN-gamma, and G-CSF. Moreover, in RRMS patients CSF concentrations of IL-1Ra and G-CSF associated with global cortical thickness. The HRF count in the inner nuclear layer (INL) correlated with IL-22, IL-34, IL-35, CXCL-2, CXCL-10, and CXCL-13, and multivariate analysis confirmed a strong association (r(2): 0.47) with both CXCL-2 (beta: -0.965, p = 0.0052) and CXCL-13 (beta: 0.241, p = 0.018). This latter cytokine increased in RRMS with high HRF count compared with NIND and RRMS with low HRF count. Finally, the CXCL-13/CXCL-2 ratio strongly associated with HRF count (r: 0.8, p < 0.005) and cortical lesion volume (r: 0.5, p < 0.05). ConclusionsThe association of HRF with intrathecally produced monocyte/microglia-derived cytokines confirms their microglial origin and indicates they are worth further evaluating as markers of activated microglia