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A few cases of multiple sclerosis (MS) onset after COVID-19 vaccination have been reported, although the evidence is insufficient to establish causality. The aim of this study is to compare cases of newly diagnosed relapsing-remitting MS before and after the outbreak of the COVID-19 pandemic and the impact of COVID-19 vaccination. Potential environmental and genetic predisposing factors were also investigated, as well as clinical patterns. This is a single-centre retrospective cohort study including all patients who presented with relapsing-remitting MS onset between January 2018 and July 2022. Data on COVID-19 vaccination administration, dose, and type were collected. HLA-DRB1 genotyping was performed in three subgroups. A total of 266 patients received a new diagnosis of relapsing-remitting MS in our centre, 143 before the COVID-19 pandemic (until and including March 2020), and 123 during the COVID-19 era (from April 2020). The mean number of new MS onset cases per year was not different before and during the COVID-19 era and neither were baseline patients' characteristics, type of onset, clinical recovery, or radiological patterns. Fourteen (11.4%) patients who subsequently received a new diagnosis of MS had a history of COVID-19 vaccination within one month before symptoms onset. Patients' characteristics, type of onset, clinical recovery, and radiological patterns did not differ from those of patients with non-vaccine-related new diagnoses of MS. The allele frequencies of HLA-DRB1*15 were 17.6% and 22.2% in patients with non-vaccine-related disease onset before and during the COVID-19 era, respectively, while no case of HLA-DRB1*15 was identified among patients with a new diagnosis of MS post-COVID-19 vaccine. In contrast, HLA-DRB1*08+ or HLA-DRB1*10+ MS patients were present only in this subgroup. Although a causal link between COVID-19 vaccination and relapsing-remitting MS cannot be detected, it is interesting to note and speculate about the peculiarities an

Background and purpose: Serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising neuro-axonal damage and astrocytic activation biomarkers. Susac syndrome (SS) is an increasingly recognized neurological condition and biomarkers that can help assess and monitor disease evolution are highly needed for the adequate management of these patients. sNfL and sGFAP levels were evaluated in patients with SS and their clinical relevance in the relapse and remission phase of the disease was assessed. Methods: As part of a multicentre study that enrolled patients diagnosed with SS from six international centres, sNfL and sGFAP levels were assessed in 22 SS patients (nine during a relapse and 13 in remission) and 59 age-and sex-matched healthy controls using SimoaTM assay Neurology 2-Plex B Kit. Results: Serum NfL levels were higher than those of healthy controls (p < 0.001) in SS patients and in both subgroups of patients in relapse and in remission (p < 0.001 for both), with significantly higher levels in relapse than in remission (p = 0.008). sNfL levels showed a negative correlation with time from the last relapse (r = -0.663; p = 0.001). sGFAP levels were slightly higher in the whole group of patients than in healthy controls (p = 0.046) and were more pronounced in relapse than in remission (p = 0.013). Conclusion: In SS patients, both sNFL and sGFAP levels increased compared with healthy controls. Both biomarkers had higher levels during clinical relapse and much lower levels in remission. sNFL was shown to be time sensitive to clinical changes and can be useful to monitor neuro-axonal damage in SS.

Ocrelizumab is a recombinant humanized monoclonal antibody selectively targeting CD20-expressing B cells. The effect of ocrelizumab on primary progressive multiple sclerosis (PPMS) has been evaluated during phase 3 trials that enrolled patients under 55 years with a maximum Expanded Disability Status Scale (EDSS) of 6.5. However, little is known on older disabled patients with longer disease duration. We aimed to assess the clinical effectiveness of ocrelizumab in PPMS patients out of the ORATORIO eligibility criteria. This multicenter retrospective study collected data about the effectiveness of ocrelizumab in PPMS patients who received treatment between May 2017 and June 2022 in the Italian MS centers contributing to the Italian MS Registry who adhered to the Compassionate Use Program. The confirmed EDSS worsening (CEW) (defined as either a ≥ 1-point or ≥ 2-point increase in EDSS score from baseline that was confirmed at T12 and T24) was calculated. At the date of data extraction, out of 887 PPMS patients who had received ocrelizumab, 589 (mean age 49.7 ± 10.7 years, 242 (41.1%) females) were enrolled. The mean follow-up period was 41.3 ± 12.3 months. A total of 149 (25.3%) received ocrelizumab according to the ORATORIO criteria (ORATORIO group) and 440 (74.7%) outside the ORATORIO criteria (non-ORATORIO group). No differences in terms of cumulative probabilities of 12 and 24 months of CEW of ≤ 1 point were found between ORATORIO and non-ORATORIO groups. Cox regression analyses showed that age older than 65 years (HR 2.51, 25% CI 1.07-3.65; p = 0.01) was associated with higher risk of CEW at 24 months. Patients not responding to ORATORIO criteria for reimbursability may benefit from ocrelizumab treatment, as disease activity, disease duration, and EDSS seem to not impact the disability outcome. Our results may suggest to extend the possible use of this powerful agent in selected patients under the age of 65 years.

Isolated cognitive relapses (ICRs) have been a matter of debate for the past few years. Currently, there is no clear consensus on such an entity, as cognitive decline usually accompanies typical multiple sclerosis (MS) relapses. Herein, we present the neuropsychological and neurophysiological manifestations of a patient who suddenly complained of confusion and memory loss, showing insight into her deficit, in absence of sensorimotor disturbances. Neuroimaging revealed a large tumefactive gadolinium-enhancing lesion localized in the left medial temporal lobe. The patient's symptoms persisted for months afterwards, despite corticosteroid treatment. We believe our patient experienced a true ICR. ICRs are rare entities in MS, but we should be alert to their existence in order to treat them promptly. Deepening their pathophysiology is equally important and neuropsychology combined with neurophysiology may be useful in this regard.

Susac syndrome (SuS) is a rare immune-mediated disorder, affecting microvessels in the brain, retina and inner ear, leading to central nervous system dysfunction, visual disturbances and sensorineural hearing loss. These events may occur simultaneously or in succession. Since its first description in 1979 by John Susac, about 400 cases have been described; however, SuS is probably underdiagnosed. SuS usually affects young adults between 20 and 40 years (female-to-male ratio of 3.5/1) [1, 2]. Occlusive microvascular endotheliopathy/basement membranopathy represents a disease hallmark, but the pathogenesis is still debated. Infections, diet or medications have been described as possible triggers of autoimmunity [1]. In 2006, a case of SuS after smallpox vaccination was reported. The COVID-19 pandemic has affected over 260 million people and different neurological disorders have been related to both Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and vaccination [3]. Six cases of SuS related to SARS-CoV-2 infection or vaccination have been described: two following SARS-CoV2 infection, one related to ChAdOx1 vaccine, and three after Coronavac vaccine [4]. Here we report the first case of SuS after BNT162b2 mRNA COVID-19 vaccine (Comirnaty®).

Several biomarkers from multiple sclerosis (MS) patients' biological fluids have been considered to support diagnosis, predict disease course, and evaluate treatment response. In this study, we assessed the CSF concentration of selected molecules implicated in the MS pathological process. To investigate the diagnostic and prognostic significance of CSF concentration of target candidate biomarkers in both relapsing (RMS, n = 107) and progressive (PMS, n = 18) MS patients and in other inflammatory (OIND, n = 10) and non-inflammatory (ONIND, n = 15) neurological disorders. We measured the CSF concentration of APRIL, BAFF, CHI3L1, CCL-2, CXCL-8, CXCL-10, CXCL-12, CXCL-13 through a Luminex Assay. MS patients were prospectively evaluated, and clinical and radiological activity were recorded. CHI3L1 and CXCL13 CSF levels were significantly higher in both MS groups compared to control groups, while CCL2, BAFF, and APRIL concentrations were lower in RMS patients compared to PMS and OIND. Considering RMS patients with a single demyelinating event, higher concentrations of CHI3L1, CXCL10, CXCL12, and CXCL13 were recorded in patients who converted to clinically defined MS(CDMS). RMS patients in the CXCL13 and CHI3L1 high concentration group had a significantly higher risk of relapse (HR 12.61 and 4.57), MRI activity (HR 7.04 and 2.46), and of any evidence of disease activity (HR 12.13 and 2.90) during follow-up. CSF CXCL13 and CHI3L1 levels represent very good prognostic biomarkers in RMS patients, and therefore can be helpful in the treatment choice. Higher CSF concentrations of neuro-inflammatory biomarkers were associated with a higher risk of conversion to CDMS in patients with a first clinical demyelinating event. Differential CSF BAFF and APRIL levels between RMS and PMS suggest a different modulation of B-cells pathways in the different phases of the disease.

Neurosarcoidosis is an uncommon and multiform clinical entity. Its presentation as an isolated longitudinal extensive transverse myelitis (LETM) is rare and challenging to identify. We report a case of LETM in a 60-year-old patient with no significant systemic symptoms nor relevant medical history. The peculiar spinal magnetic resonance imaging finding characterized by a posterior and central canal subpial contrast enhancement, the so-called "trident sign," together with chest computed tomography scan and lymph node biopsy led to the diagnosis of sarcoidosis. We also discuss the main differential diagnoses of LETM and therapeutic options for sarcoidosis-related myelitis.

Introduction: The complexity of the MS patient's management is constantly growing. Consequently, the MS care unit requires a multidisciplinary approach, including an infectious disease specialist to minimise the risk of infectious complications related both to the disease and DMTs. Materials and methods: We retrospectively evaluated the infectious disease consultations performed from 2015 to 2019 in our MS centre. Results: We identified 107 patients with at least one infectious disease consultation out of 1088 patients. We found a progressive increase in the number of consultations from 2015 to 2019. Nearly half of the consultations were requested at the time of starting MS treatment. The most frequent requests were represented by chronic or acute infections. The most prevalent infectious agents were Herpesviridae and Mycobacterium tuberculosis. Antibiotic or antiviral treatment and prophylactic treatment or vaccination represented together the most frequent outcomes of the consultations. Finally, a treatment delay was significantly associated with the advice of a prophylactic treatment or of a vaccination. Conclusion: There is an increasing awareness of the potential infectious complications of MS and of exposure to DMTs. The interaction between the MS neurologist and infectious disease specialist is fundamental to minimise the infectious risk related to the disease and to the DMTs, with a progressive shift from complication management to a broader prevention workup at the time of MS diagnosis, including both vaccination and prophylactic treatments.

The original version of this article unfortunately contained a mistake. The given and family names of authors were Interchanged except the following author Maria Chiara Buscarinu, Carolina Gabri Nicoletti, Alessandra Girolama Marfia and Antonio Gallo.