Breakthrough COVID-19 in people with multiple sclerosis on disease modifying treatments: Is it still a severe disease?

INTRODUCTION: Disease modifying treatments (DMTs) for multiple sclerosis (MS) are effective in preventing both relapses and disability progression. Highly effective treatments (HETs) are more effective than platform therapy in preventing confirmed disability progression (CDP), when used early. Infections may complicate HETs administration, and their prevention through vaccination is crucial in order to assure the safety of people with MS (pwMS). The aim of the present study is to describe the effect of MS DMTs on COVID-19 vaccination and the risk of breakthrough infection in a cohort of pwMS. MATERIALS AND METHODS: This is a monocentric retrospective observational study conducted at the MS center of the Guglielmo da Saliceto Hospital in Piacenza, Italy. One hundred and fifty-seven (157) pwMS who received two doses of the SARS-CoV-2 vaccine (with 80.3 % receiving a booster dose) were included in the study. RESULTS: fifty-six pwMS (35.7 %) were females, the mean age was 48.6 (SD: 12.87) years, and 59 (37.6 %) had at least one comorbidity. Twenty-five (15.9 %) breakthrough infections were observed, with 17 (68.0 %) classified as mild and 8 (32.0 %) as moderate. A multivariable linear regression model confirmed that B-cell suppressor DMTs and EDSS were factors associated with the latest antibody titre. Patients treated with B-cell suppressors exhibited a risk almost four times higher for breakthrough infections compared to other patients, with a hazard ratio (HR) of 3.72 (95 % CI: 1.50 - 9.27) (p = 0.005). CONCLUSIONS: B-cell suppressor DMTs are associated with the risk of breakthrough COVID-19 in our cohort, but vaccination fully protected pwMS against severe breakthrough disease.

Sex differences in ischemic stroke during COVID-19 first outbreak in northern Italy.

INTRODUCTION: COVID-19 pandemic had a great impact on outcome in SARS-CoV-2 positive patients with ischemic stroke during the first wave in Italy. Few data are available on outcome stratified by sex. METHODS: The Italian Society of Hospital Neuroscience conducted a multi-center, retrospective, observational study on neurological complications in COVID-19 patients with ischemic stroke. All the patients admitted from March 1st to April 30th, 2020 in 20 Neurology Units in Northern Italy were recruited. Demographical and clinical features, treatment and outcome data were compared focusing on sex differences. RESULTS: 812 patients with ischemic stroke were enrolled, of whom 129 with COVID-19; males were 53.8%. In-hospital mortality in COVID-19 patients was 35.3% in males and 27.9% in females while 8.5% in male and 5.8% in female patients without COVID-19. SARS-CoV-2 positive patients had a higher frequency of stroke of undetermined etiology, than negative ones (32.8% vs 22.5%; p = 0.02), especially in females compared to males (36.1% vs 27.9%), albeit without statistical significance. Male patients with SARS-CoV-2 were more likely to require cPAP (30.9% vs 14.8%; p = 0.03), endotracheal tube (14.9% vs 3.3%; p = 0.02) and reperfusion strategies (29.4% vs 11.5%; p = 0.01) than females, as well as to have a higher CRP and D-dimer. These elements together with older age, a total anterior circulation stroke and lymphopenia were predictors of a worse outcome. DISCUSSION: Our study detected some differences due to sex in ischemic stroke with and without COVID-19, supporting the possibility to perform sex analyses for SARS-CoV-2 positive patients for a better clinical management.

CT perfusion extended window ischemic core estimation: Bayesian algorithm versus oscillation index singular value decomposition.

BACKGROUND AND PURPOSE: Ischemic core estimation by CT perfusion (CTp) is a diagnostic challenge, mainly because of the intrinsic noise associated with perfusion data. However, an accurate and reliable quantification of the ischemic core is critical in the selection of patients for reperfusion therapies. Our study aimed at assessing the diagnostic accuracy of two different CTp postprocessing algorithms, that is, the Bayesian Method and the oscillation index singular value decomposition (oSVD). METHODS: All the consecutive stroke patients studied in the extended time window (>4.5 hours from stroke onset) by CTp and diffusion-weighted imaging (DWI), between October 2019 and December 2021, were enrolled. The agreement between both algorithms and DWI was assessed by the Bland-Altman plot, Wilcoxon signed-rank test, Spearman's rank correlation coefficient, and the intraclass correlation coefficient (ICC). RESULTS: Twenty-four patients were enrolled (average age: 72 ± 15 years). The average National Institutes of Health Stroke Scale was 14.42 ± 6.75, the median Alberta Stroke Program Early CT score was 8.50 (interquartile range [IQR] = 7.75-9), and median time from stroke onset to neuroimaging was 7.5 hours (IQR = 6.5-8). There was an excellent correlation between DWI and oSVD (ρ = .87, p-value < .001) and DWI and Bayesian algorithm (ρ = .94, p-value < .001). There was a stronger ICC between DWI and Bayesian algorithm (.97, 95% confidence interval [CI]: .92-.99, p-value < .001) than between DWI and oSVD (.59, 95% CI: .26-.8, p-value < .001). DISCUSSION: The agreement between Bayesian algorithm and DWI was greater than between oSVD and DWI in the extended window. The more accurate estimation of the ischemic core offered by the Bayesian algorithm may well play a critical role in the accurate selection of patients for reperfusion therapies.

The Impact of Highly Effective Treatment in Pediatric-Onset Multiple Sclerosis: A Case Series.

INTRODUCTION: Pediatric-onset multiple sclerosis (POMS) is characterized by high inflammatory disease activity. Our aim was to describe the treatment sequencing and report the impact highly effective disease-modifying treatment (HET) had on disease activity. MATERIALS AND METHODS: Five consecutive patients with POMS were administered HET following lower efficacy drug or as initial therapy. Data on treatment sequencing, relapses and MRIs were collected during the follow-up. RESULTS: Our patients had an average age of 13.8 years (range 9-17) at diagnosis and 13.4 years (range 9-16) at disease onset, and 2/5 (40%) POMS were female. The pre-treatment average annualized relapse rate was 1.6 (range 0.8-2.8), and the average follow-up length was 5 years (range 3-7). A total of 2/5 (40%) patients were stable on HET at initial therapy, and 3/5 (60%) required an escalation to more aggressive treatment, even if two of them had been put on HET as initial treatment. Four out of five patients (80%) had No Evidence of Disease Activity-3 status (NEDA-3) at an average follow-up of 3 years (range 2-5). CONCLUSION: It has been observed that in a recent time period all the cases had prompt diagnosis, early HET or escalation to HET with a good outcome in 80% of the cases.

A "Post-mortem" of COVID-19-associated stroke: a case-control study.

OBJECTIVES: To assess whether COVID-19 could be a concurrent factor in the genesis and/or worsening of stroke and to provide data on COVID-19 -associated stroke patients during the first pandemic wave and comparative data on COVID-19 negative stroke patients in the same period. MATERIALS AND METHODS: This is a retrospective, observational, case-control, single centre study, carried out in a General Hospital in northern Italy. Sixty-three consecutive stroke patients were included, COVID-19-associated stroke was classified as cases and non COVID-19-associated stroke as controls. RESULTS: A total of 19/63 (28.8%) had a COVID-19-associated stroke, 11 /63 (17.5%) were haemorrhagic and 52/63 (82.5%) ischaemic. COVID-19-associated strokes were more severe (p-value 0.019) and had a higher risk of severe disability and/or death (OR 3.79, CI 95%: 1.21-11.93, p-value 0.19). The COVID-19-associated stroke patients with onset during hospitalization for COVID-19 had a more severe stroke than patients with COVID-19 onset during hospitalization for stroke (p-value 0.019). CONCLUSION: Although no relationship was observed between the stroke aetiology and COVID-19, intriguingly, COVID-associated stroke turned out to be more severe and disabling. Hopefully, further studies will provide more data and help in the management of this emerging population.

Lung involvement correlates with disability in MS patients with COVID-19 pneumonia.

INTRODUCTION: The visual-well aerated lung (V-WAL) is a score for the visual quantification of the well aerated lung on CT scan in COVID-19 patients and its value at admission seems to predict future COVID-19 severity. The aim of the present study was to analyze the association between V-WAL and risk factors for severe COVID-19 evolution in people with multiple sclerosis. MATERIALS AND METHODS: This is an observational retrospective study, including people with multiple sclerosis and concomitant COVID-19, who were investigated with a lung CT scan at Hospital admission. The association of V-WAL with age, sex, EDSS, comorbidities, recent steroid use, and treatment (anti-CD20 vs other) was assessed by a multivariate linear regression model. RESULTS: In this observational retrospective study, the only factor that was significantly associated to a lower V-WAL at multivariable analysis was an increasing level of the EDSS (R2 = 0.41, p = 0.001), with an average decrease of 8% of V-WAL for each additional EDSS point. DISCUSSION AND CONCLUSION: This analysis shows that a high EDSS level is the main factor associated to the severity of lung involvement in a group of people with multiple sclerosis who were hospitalized for Covid-19.

Epidemiological, Clinical and Genetic Features of ALS in the Last Decade: A Prospective Population-Based Study in the Emilia Romagna Region of Italy.

Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype-phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS. The age- and sex-adjusted incidence rate was 3.13/100,000 population (M/F ratio: 1.21). The mean age at onset was 67.01 years; women, bulbar and respiratory phenotypes were associated with an older age, while C9orf72-mutated patients were generally younger. After peaking at 70-75 years, incidence rates, among women only, showed a bimodal distribution with a second slight increase after reaching 90 years of age. Familial cases comprised 12%, of which one quarter could be attributed to an ALS-related mutation. More than 70% of C9orf72-expanded patients had a family history of ALS/fronto-temporal dementia (FTD); 22.58% of patients with FTD at diagnosis had C9orf72 expansion (OR 6.34, p = 0.004). In addition to a high ALS incidence suggesting exhaustiveness of case ascertainment, this study highlights interesting phenotype-genotype correlations in the ALS population of ERR.

Multiple Sclerosis Treatment in the COVID-19 Era: A Risk-Benefit Approach.

The COVID-19 pandemic poses an ongoing global challenge, and several risk factors make people with multiple sclerosis (pwMS) particularly susceptible to running a severe disease course. Although the literature does report numerous articles on the risk factors for severe COVID-19 and vaccination response in pwMS, there is a scarcity of reviews integrating both these aspects into strategies aimed at minimizing risks. The aim of this review is to describe the risk of vulnerable pwMS exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues related to the SARS-CoV-2 vaccine and to evidence possible future strategies in the clinical management of pwMS. The authors searched for papers on severe COVID-19 risk factors, SARS-CoV-2 vaccination and people with multiple sclerosis in support of this narrative literature review. We propose a multilevel strategy aimed at: the evaluation of risk factors for severe COVID-19 in people with multiple sclerosis, identifying the most appropriate vaccination schedule that is safe for people on disease-modifying drugs (DMDs) and a strict follow-up of high-risk people with multiple sclerosis to allow for the prompt administration of monoclonal antibodies to manage COVID-19 risks in this patient population.

Fabry-Stroke Italian Registry (FSIR): a nationwide, prospective, observational study about incidence and characteristics of Fabry-related stroke in young-adults. Presentation of the study protocol.

BACKGROUND: TIA and stroke, both ischemic and hemorrhagic, may complicate Fabry disease at young-adult age and be the first manifestation that comes to the clinician's attention. No definite indications have yet been elaborated to guide neurologists in Fabry disease diagnostics. In current practice, it is usually sought in case of cryptogenic strokes (while Fabry-related strokes can also occur by classical pathogenic mechanisms) or through screening programs in young cerebrovascular populations. Data on recurrence and secondary prevention of Fabry's stroke are scanty. METHODS: The study had a prospective observational design involving 33 Italian neurological Stroke Units. Considering the incidence of TIA/stroke in the European population aged < 60 years and the frequency of Fabry disease in this category (as foreseen by a pilot study held at the Careggi University-Hospital, Florence), we planned to screen for Fabry disease a total of 1740 < 60-year-old individuals hospitalized for TIA, ischemic, or hemorrhagic stroke. We investigated TIA and stroke pathogenesis through internationally validated scales and we gathered information on possible early signs of Fabry disease among all cerebrovascular patients. Every patient was tested for Fabry disease through dried blood spot analysis. Patients who received Fabry disease diagnosis underwent a 12-month follow-up to monitor stroke recurrence and multi-system progression after the cerebrovascular event. DISCUSSION: The potential implications of this study are as follows: (i) to add information about the yield of systematic screening for Fabry disease in a prospective large cohort of acute cerebrovascular patients; (ii) to deepen knowledge of clinical, pathophysiological, and prognostic characteristics of Fabry-related stroke.

Impact of SARS-CoV-2 infection on acute intracerebral haemorrhage in northern Italy.

INTRODUCTION: Growing evidence has been published as to the impact of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) on cerebrovascular events over the last few months, with considerable attention paid to ischemic strokes. Conversely, little is known about the clinical course of intracerebral haemorrhage (ICH) and simultaneous SARS-CoV-2 infection. METHOD: The Italian Society of Hospital Neurosciences (SNO) promoted a multicentre, retrospective, observational study (SNO-COVID-19), involving 20 Neurological Departments in Northern Italy. Clinical data on patients with acute cerebrovascular diseases, admitted from March 1st to April 30th, 2020, were collected. A comparison was made of the demographical and clinical features of both SARS-CoV-2 positive and negative patients with ICH. RESULTS: 949 patients were enrolled (average age 73.4 years; 52.7% males); 135 patients had haemorrhagic stroke and 127 (13.4%) had a primary ICH. Only 16 patients with ICH (12.6%) had laboratory confirmed SARS-CoV-2 infection, both symptomatic and asymptomatic. SARS-CoV-2 related pneumonia or respiratory distress (OR 5.4), lobar location (OR 5.0) and previous antiplatelet or anticoagulant treatment (OR 2.9) were the only factors significantly associated with increased mortality in ICH. SARS-CoV-2 infection, regardless of respiratory involvement, led to a non-significantly increased risk of in-hospital death (37.5% vs 23.4%, p = 0.2). DISCUSSION: ICH patients with COVID-19 did not experience an increase in mortality as striking as ischemic stroke. The inflammatory response and respiratory complications could justify the slight increase of death in ICH. Bleeding sites and previous antiplatelet or anticoagulant treatment were the only other predictors of a worse outcome.

Two-year follow-up during fingolimod treatment in a pediatric multiple sclerosis patient still active on first-line treatment.

Treatment of pediatric multiple sclerosis (MS) has been increasingly debated in the last few years due to limited knowledge of treatment strategies and therapeutic options. When MS develops at a young age, it usually has a very inflammatory disease course, with many relapses and disease activity as seen in magnetic resonance imaging (MRI). Therefore, treatment with immunomodulatory drugs may be beneficial in these patients. However, limited data are available to date on the treatment of pediatric MS. Although observational, prospective, and retrospective studies provide some information on its treatment course, only one clinical trial in pediatric patients has been published, the PARADIGMS trial, which showed an 82% reduction in relapse rate with fingolimod (0.5 mg/day) versus interferon ß-1a (30 µg once weekly intramuscularly). Here, we present the case of a pediatric patient with MS (age of onset, 13 years), who was initially treated with interferon ß-1a for 2 years and subsequently switched to fingolimod, owing to clinical and radiological activity despite treatment with interferon ß-1a.

Diagnostic Accuracy of a Bedside Screening Tool for Dysphagia (BSTD) in Acute Stroke Patients.

BACKGROUND AND PURPOSE: an estimated 40-80% of acute ischemic stroke patients have dysphagia and about 14% develop stroke-associated pneumonia. However, it may be difficult to detect swallowing problems at admission. Moreover, there might not be an on-duty specialist skilled in the diagnosis of this condition. This study aimed at developing a user-friendly bedside examination to identify the risk of dysphagia in stroke patients at hospital admission. METHODS: a diagnostic accuracy study was carried out to assess the concurrent validity of a simple Bedside Screening Tool for Dysphagia (BSTD) in acute stroke. All the consecutive stroke patients admitted between January and April 2018 were enrolled. Sensitivity, specificity, positive (PPV), negative predictive values (NPV) and the Cohen K concordance index scores, reported by nurses and speech-pathologists, were assessed. RESULTS: a total of 67/120 patients (55.8%) were male; overall average age was 67.4 (range 45-91) and 80.8% of the whole population had a history of ischemic stroke. The nursing staff identified 33.3% of dysphagia cases at admission and the speech pathologists 30%. The Cohen K was 0.92 (optimal concordance when K was > 0.8), sensitivity was 100%, specificity 95.2%, PPV 90% and NPV 100%. CONCLUSIONS: our BSTD had a 100% negative predictive value, indicating that this screening test is very useful in ruling out/confirming dysphagia in acute stroke patients.

Lactate dehydrogenase and C-reactive protein as predictors of respiratory failure in CoVID-19 patients.

OBJECTIVE: The dramatic worldwide CoVID-19 infection requires the identification of a reliable and inexpensive tool to quickly discriminate patients with a more unfavorable outcome. METHODS: We performed routine laboratory tests suitable to identify tissue damage and inflammatory status in 123 consecutive CoVID-19 patients admitted to the Emergency Department of the hospital of Piacenza (Emilia-Romagna, Northern Italy). The results were correlated with patients' respiratory function evaluated by the partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2). RESULTS: The most common laboratory abnormalities were lymphocytopenia and elevated values of C-reactive protein (CRP) and lactate dehydrogenase (LDH). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) were also increased. The respiratory performance (PaO2/FiO2) showed a strong inverse correlation with LDH (r = 0.62, r2 0.38, p value < 0.0001) and CRP (r = 0.55, r2 0.31, p value < 0.0001). PaO2/FiO2 values also showed a significant inverse correlation with age (r = -0.37, p < 0.0001), AST (r = -0.31, p < 0.01), WBC (r = -0.49, p < 0.0001), neutrophils count (r = -0.5, p < 0.001). ROC curves showed a sensitivity of 75% and specificity of 70% for the LDH cut-off value of 450 U/L and a sensitivity of 72% and specificity of 71% for the CRP cut-off value of 11 mg/dl in identifying CoVID-19 with moderate-severe ARDS. CONCLUSIONS: LDH and CRP may be related to respiratory function (PaO2/FiO2) and be a predictor of respiratory failure in CoVID-19 patients. LDH and CRP should be considered a useful test for the early identification of patients who require closer respiratory monitoring and more aggressive supportive therapies to avoid poor prognosis.