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Here we described the virological and serological assessment of 23 COVID-19 patients hospitalized and followed up in Milan, Italy, during the first wave of COVID-19 pandemic. Nasopharyngeal (NPS), anal swabs, and blood samples were collected from 23 COVID-19 patients, at hospital admission, and periodically up to discharge, for a median time of 20 days (3-83 days). RNA was isolated and tested for SARS-CoV-2 by qRT-PCR; anti-SARS-CoV-2 IgM and IgG antibody titers were evaluated in serum samples by ELISA. SARS-CoV-2 genome was detected in the NPS swabs of the 23 patients, at the admission, and 8/19 (42.1%) were still positive at the discharge. Anal swabs were positive to SARS-CoV-2 RNA detection in 20/23 (86.9%) patients; 6/19 (31.6%) were still positive at discharge. The mean time of RNA negative conversion was 17 days (4-36 days) and 33 days (4-77 days), for NPS and anal swabs, respectively. SARS-CoV-2-RNA was detected in the blood of 6/23 (26.1%) patients. Thirteen/23 (56.5%) and 17/23 (73.9%) patients were seropositive for IgM and IgG, respectively, at the admission, and the median IgM and IgG levels significantly (p < 0.05) increased after 13 days. Although the limited cohort size, our report provides evidence that SARS-CoV-2 is shed through multiple routes, with important implications in healthcare settings., (© 2021. Journal of NeuroVirology, Inc.)

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL., Methods: Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities., Results: 128 patients (mean age 56.3 ± 12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity., Conclusions: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield.

Background and Purpose: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease, Methods: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis., Results: In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease., Conclusions: In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series., (© 2016 American Heart Association, Inc.)

Background: Recombinant interferons have been approved by many national regulatory agencies for treatment of relapsing remitting multiple sclerosis, but widespread discussion continues about their true effectiveness, benefits, side-effects, and costs., Methods: With the Cochrane Collaboration methodology, we reviewed all published, randomised, placebo-controlled trials of recombinant interferons undertaken in patients with relapsing remitting multiple sclerosis between 1993 and 2002. Our primary aim was to find out whether recombinant interferons reduced the number of patients who had clinical exacerbations and disease progression, compared with placebo., Findings: The seven trials that met our criteria included 1215 randomised patients: data from 667 (55%) were available for analysis at 1 year's and from 919 (76%) at 2 years' follow-up. Interferon seemed to reduce the number of patients who had exacerbations during the first year of treatment (relative risk 0.73, 95% CI 0.54-0.99), but results at 2 years' follow-up were not robust and were difficult to interpret because of the many dropouts. Although the number of patients who had exacerbations (0.81, 0.74-0.89) or progressed (0.70, 0.55-0.88) during the first 2 years fell significantly in the protocol analysis, results were inconclusive after sensitivity analyses for exacerbations (1.11, 0.73-1.68) and disease progression (1.31, 0.60-2.89). Data were insufficient to establish whether steroid use and admissions to hospital were reduced in the interferon group. Similarly, MRI outcome data could not be analysed quantitatively. Side-effects were common, and acute toxic effects adversely affected quality of life., Interpretation: Recombinant interferons slightly reduce the number of patients who have exacerbations during first year of treatment. Their clinical effect beyond 1 year is uncertain and new trials are needed to assess their long-term effectiveness and side-effects.

Background: Multiple sclerosis is a presumed cell-mediated autoimmune disease of the central nervous system. Cyclophosphamide (CFX) is a cytotoxic and immunosuppressive agent, used in systemic autoimmune diseases. Controversial results have been reported on its efficacy in MS. We conducted a systematic review of all relevant trials, evaluating the CFX efficacy in patients with progressive MS., Objectives: The main objectives were to determine whether CFX slows the disease progression., Search Strategy: Electronic databases (including MEDLINE, EMBASE, Cochrane Controlled Trials Register) were systematically searched. References list of retrieved studies and conference abstracts on the main meetings on Multiple Sclerosis were handsearched., Selection Criteria: Randomised controlled trials (RCTs) evaluating the clinical effect of CFX treatment in patients affected by clinically definite progressive MS. CFX had to be administered alone or in combination with ACTH or steroids. The comparison group had to be placebo or no treatment or the same co intervention (ACTH or steroids) The main outcome criteria were : progression of disability (defined as an increase of 0.5 point in Kurtzke Extended Disability Status Scale (EDSS) for patients with baseline EDSS > or = 6 and 1 for EDSS < or = 5.5), differences of disability between treatment-control groups and the number of patients with side effects., Data Collection and Analysis: The identified references were reviewed by two reviewers who independently decided the eligibility of the study, extracted and summarized data and assessed the trial's quality. The statistical analysis was performed using the Cochrane RevMan software and analyzed using Cochrane MetaView., Main Results: Of the 326 identified references, 80 were selected for full review, only four RCTs were selected for the final analysis. Intensive immunosuppression with CFX (alone or associated with ACTH or prednisone) in patients with progressive MS compared to placebo or no-treatment (152 participants) did not prevent the long -term (12-18-24 months) risk to evolution to a next step of EDSS. However, the mean change in disability (final disability subtracted from the baseline) significantly favoured the treated group at 12 (effect size - 0.21; C. I. - 0.24, - 0.17) and 18 months (- 0.19; C. I. - 0.24, - 0.14). We were not able to verify the efficacy of other schedules. Five patients died; sepsis and amenorrhea frequently occurred in treated patients (descriptive analysis)., Reviewer's Conclusions: Only limited objectives were reached. This review shows a role of CFX in the treatment of progressive MS, but less toxic schedules must be considered, before its use in the clinical practice.

Background: Recombinant interferons have been shown to suppress both the clinical and magnetic resonance imaging (MRI) measures of disease activity in patients with relapsing remitting multiple sclerosis (RRMS)., Objectives: We performed a Cochrane review of all randomised, placebo-controlled trials of recombinant interferons in RRMS., Search Strategy: Of 208 articles identified by a predefined search strategy, seven of these, reporting randomised trials, met all the selection criteria and form the subject of this review., Selection Criteria: The trials selected were double-blind, placebo-controlled, randomised trials of RRMS patients who were treated with recombinant interferon, given by the subcutaneous or the intramuscular route., Data Collection and Analysis: The quality of the trials was variable, with substantial methodological inadequacies in allocation concealment, high proportion and incomplete description of dropouts and failure to adhere to the principles of intention to treat analysis. The baseline characteristics were largely comparable between treatment and placebo groups. Because of prominent treatment-associated side effects, which could be easily identified by patients, these trials could be considered as single blind rather than double-blind., Main Results: Although 1215 patients were included in this review, only 919 (76%) contributed to the results concerning exacerbations and progression of the disease at two years. Specifically interferon significantly reduced the occurrence of exacerbations (RR =0.80, 95% CI [0.73,0.88], p<0.001) and progression of the disease (RR =0.69, 95% CI [0.55,0.87], p= 0.002) two years after randomisation. However, the correct assignment of dropouts was essential to the demonstration of efficacy, most conspicuously concerning the effect of the drug on disease progression. If interferon-treated patients who dropped out were deemed to have progressed (worst case scenario) the significance of these effects was lost (RR = 1.31, CI [0.60,2.89], p = 0.5). The evolution in magnetic resonance imaging (MRI) technology in the decade in which these trials were performed and different reporting of data among trials made it impossible to perform a quantitative analysis of the MRI results. Both clinical and laboratory side effects reported in the trials were more frequent in treated patients than in controls. No information was available regarding side effects and adverse events after two years of follow-up. The impact of interferon treatment (and its side effects) on the quality of life of patients was not reported in any trial included in this review., Reviewer's Conclusions: The efficacy of interferon on exacerbations and disease progression in patients with relapsing remitting MS was modest after one and two years of treatment. It was not possible to conduct a quantitative analysis beyond two years. Longer follow-up and more uniform reporting of clinical and MRI outcomes among these trials might have allowed for a more convincing conclusion.