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.

In the early phases of relapsing-remitting multiple sclerosis (RR-MS), a clear correlation between brain lesion load and clinical disability is often lacking, originating the so-called clinico-radiological paradox. Different factors may contribute to such discrepancy. In particular, synaptic plasticity may reduce the clinical expression of brain damage producing enduring enhancement of synaptic strength largely dependent on neurotrophin-induced protein synthesis. Cytokines released by the immune cells during acute inflammation can alter synaptic transmission and plasticity possibly influencing the clinical course of MS. In addition, immune cells may promote brain repair during the post-acute phases, by secreting different growth factors involved in neuronal and oligodendroglial cell survival. Platelet-derived growth factor (PDGF) is a neurotrophic factor that could be particularly involved in clinical recovery. Indeed, PDGF promotes long-term potentiation of synaptic activity in vitro and in MS and could therefore represent a key factor improving the clinical compensation of new brain lesions. The aim of the present study is to explore whether cerebrospinal fluid (CSF) PDGF concentrations at the time of diagnosis may influence the clinical course of RR-MS. At the time of diagnosis, we measured in 100 consecutive early MS patients the CSF concentrations of PDGF, of the main pro- and anti-inflammatory cytokines, and of reliable markers of neuronal damage. Clinical and radiological parameters of disease activity were prospectively collected during follow-up. CSF PDGF levels were positively correlated with prolonged relapse-free survival. Radiological markers of disease activity, biochemical markers of neuronal damage, and clinical parameters of disease progression were instead not influenced by PDGF concentrations. Higher CSF PDGF levels were associated with an anti-inflammatory milieu within the central nervous system. Our results suggest that PDGF could promote a more prolonged relapse-free period during the course of RR-MS, without influencing inflammation reactivation and inflammation-driven neuronal damage and likely enhancing adaptive plasticity.

To describe the heterogeneity of electrodiagnostic (EDx) studies in Guillain-Barré syndrome (GBS) patients collected as part of the International GBS Outcome Study (IGOS). Prospectively collected clinical and EDx data were available in 957 IGOS patients from 115 centers. Only the first EDx study was included in the current analysis. Median timing of the EDx study was 7 days (interquartile range 4-11) from symptom onset. Methodology varied between centers, countries and regions. Reference values from the responding 103 centers were derived locally in 49%, from publications in 37% and from a combination of these in the remaining 15%. Amplitude measurement in the EDx studies (baseline-to-peak or peak-to-peak) differed from the way this was done in the reference values, in 22% of motor and 39% of sensory conduction. There was marked variability in both motor and sensory reference values, although only a few outliers accounted for this. Our study showed extensive variation in the clinical practice of EDx in GBS patients among IGOS centers across the regions. Besides EDx variation in GBS patients participating in IGOS, this diversity is likely to be present in other neuromuscular disorders and centers. This underlines the need for standardization of EDx in future multinational GBS studies.

Background and Objectives To investigate the longitudinal dynamic of lymphocyte subsets during treatment with ocrelizumab (OCR) in patients with multiple sclerosis (PwMS). Methods A multicenter retrospective study was conducted in 161 PwMS starting treatment with OCR grouped in naive (naive, n = 40), switching from fingolimod (FTY, n = 52), and switching from other immunomodulating drugs (other, n = 69). Mean lymphocyte subset (total, CD3⁺, CD4⁺, CD8⁺, CD20⁺, and natural killer) counts were analyzed at baseline, 6 months, and 12 months. Rate of lymphocytopenia for each subset was calculated at all time points in all groups. Results Mean total, CD3⁺, and CD4⁺ counts were significantly different among groups (p < 0.001) at all time points, whereas CD8⁺ and CD20⁺ counts only at baseline (p = 0.0157; p < 0.001), consistently lower in FTY. After adjustment for baseline values, interaction time*group was not statistically significant (p > 0.05 for each subset). The odds of lymphopenia were significantly higher among FTY patients compared with naive for total, CD3⁺, CD4⁺, and CD20⁺ cells at baseline, for total and CD4⁺ cells at the sixth month, and for total cells at the 12th month. Discussion OCR per se exerts a modest depleting effect on T cells that seems rather due to a carryover phenomenon of previous therapies, particularly FTY. These data may help in the overall evaluation of the risk/benefit profile of treatment sequencing.

The involvement of macular preganglionic elements’ function, during the neurodegenerative process of multiple sclerosis (MS), is controversial. In this case-control observational and retrospective study, we assessed multifocal electroretinogram (mfERG) responses from 41 healthy Controls, 41 relapsing-remitting MS patients without optic neuritis (ON) (MS-noON Group) and 47 MS patients with ON: 27 with full recovery of high-contrast best corrected visual acuity (BCVA) (MS-ON-G Group) and 20 with poor recovery (between 0.2 and 1 LogMAR) of BCVA, (MS-ON-P Group). In the latter Group, Sd-OCT macular volumes and thicknesses of whole and inner and outer retina were measured. MfERG N1 and P1 implicit times (ITs), and N1-P1 response amplitude densities (RADs), were measured from concentric rings (R) with increasing foveal eccentricity: 0–5° (R1), 5–10° (R2), 10–15° (R3), 15–20° (R4), 20–25° (R5), and from retinal sectors (superior, nasal, inferior and temporal) between 0–15° and 0–25°. In the MS-ON-P Group, mean mfERG RADs detected from R1 (0–5°) and from the central nasal sector (0–15°) were significantly reduced (p < 0.01) with respect to those of the Control, MS-noON and MS-ON-G Groups. No other significant differences between Groups for any mfERG parameters were found. All Sd-OCT measurements, apart from the inner retina macular volume in the central 1 mm, were significantly reduced in MS-ON-P patients compared to Controls. The functional impairment in the MS-ON-P Group was associated but not correlated with structural changes of the outer and inner retinal layers in corresponding retinal Areas and Sectors. Our results suggest that in MS, exclusively after ON with poor recovery of BCVA, the neurodegenerative process can induce dysfunctional mechanisms involving photoreceptors and bipolar cells of the fovea and of the more central nasal macular area.