Publications by authors named "Sara La Gioia"

14 Publications

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SARS-CoV-2 infection and acute ischemic stroke in Lombardy, Italy.

J Neurol 2021 May 24. Epub 2021 May 24.

Department of Neurology and Stroke Unit, Carlo Poma Hospital, ASST Mantova, Mantova, Italy.

Objective: To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients.

Methods: In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19.

Results: Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06-2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05-2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS score, 9 (25th to75th percentile, 13) vs 6 (25th to75th percentile, 9)] and increased risk of in-hospital death (38.1% deaths vs 7.2%; HR 3.30; 95% CI 2.17-5.02). The RF model based on six clinical and laboratory parameters exhibited high cross-validated classification accuracy (0.86) and precision (0.87), good recall (0.72) and F1-score (0.79) in predicting in-hospital death.

Conclusions: Ischemic strokes in COVID-19 patients have distinctive risk factor profile and etiology, increased clinical severity and higher in-hospital mortality rate compared to non-COVID-19 patients. A simple model based on clinical and routine laboratory parameters may be useful in identifying ischemic stroke patients with SARS-CoV-2 infection who are unlikely to survive the acute phase.
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http://dx.doi.org/10.1007/s00415-021-10620-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142879PMC
May 2021

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

J Neurol Sci 2021 Jul 5;426:117479. Epub 2021 May 5.

Neurological Department, "Alessandro Manzoni" Hospital, ASST Lecco, Via dell'Eremo 9/11, 23900 Lecco, 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.
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http://dx.doi.org/10.1016/j.jns.2021.117479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096523PMC
July 2021

Impact of SARS-CoV-2 on reperfusion therapies for acute ischemic stroke in Lombardy, Italy: the STROKOVID network.

J Neurol 2021 Mar 8. Epub 2021 Mar 8.

Department of Neurology and Stroke Unit, Carlo Poma Hospital, ASST Mantova, Mantua, Italy.

Whether and how SARS-CoV-2 outbreak affected in-hospital acute stroke care system is still matter of debate. In the setting of the STROKOVID network, a collaborative project between the ten centers designed as hubs for the treatment of acute stroke during SARS-CoV-2 outbreak in Lombardy, Italy, we retrospectively compared clinical features and process measures of patients with confirmed infection (COVID-19) and non-infected patients (non-COVID-19) who underwent reperfusion therapies for acute ischemic stroke. Between March 8 and April 30, 2020, 296 consecutive patients [median age, 74 years (interquartile range (IQR), 62-80.75); males, 154 (52.0%); 34 (11.5%) COVID-19] qualified for the analysis. Time from symptoms onset to treatment was longer in the COVID-19 group [230 (IQR 200.5-270) minutes vs. 190 (IQR 150-245) minutes; p = 0.007], especially in the first half of the study period. Patients with COVID-19 who underwent endovascular thrombectomy had more frequently absent collaterals or collaterals filling ≤ 50% of the occluded territory (50.0% vs. 16.6%; OR 5.05; 95% CI 1.82-13.80) and a lower rate of good/complete recanalization of the primary arterial occlusive lesion (55.6% vs. 81.0%; OR 0.29; 95% CI 0.10-0.80). Post-procedural intracranial hemorrhages were more frequent (35.3% vs. 19.5%; OR 2.24; 95% CI 1.04-4.83) and outcome was worse among COVID-19 patients (in-hospital death, 38.2% vs. 8.8%; OR 6.43; 95% CI 2.85-14.50). Our findings showed longer delays in the intra-hospital management of acute ischemic stroke in COVID-19 patients, especially in the early phase of the outbreak, that likely impacted patients outcome and should be the target of future interventions.
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http://dx.doi.org/10.1007/s00415-021-10497-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937781PMC
March 2021

Neurologic manifestations in 1760 COVID-19 patients admitted to Papa Giovanni XXIII Hospital, Bergamo, Italy.

J Neurol 2021 Jul 7;268(7):2331-2338. Epub 2020 Oct 7.

Department of Neurology, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127, Bergamo, Italy.

Objectives: Evidences from either small series or spontaneous reporting are accumulating that SARS-CoV-2 involves the Nervous Systems. The aim of this study is to provide an extensive overview on the major neurological complications in a large cohort of COVID-19 patients.

Methods: Retrospective, observational analysis on all COVID-19 patients admitted from February 23rd to April 30th, 2020 to ASST Papa Giovanni XXIII, Bergamo, Italy for whom a neurological consultation/neurophysiological assessment/neuroradiologic investigation was requested. Each identified neurologic complication was then classified into main neurologic categories.

Results: Of 1760 COVID-19 patients, 137 presented neurologic manifestations that manifested after COVID-19 symptoms in 98 pts and was the presenting symptom in 39. Neurological manifestations were classified as: (a) cerebrovascular disease [53 pts (38.7%)] including 37 ischemic and 11 haemorrhagic strokes, 4 transient ischemic attacks, 1 cerebral venous thrombosis; (b) peripheral nervous system diseases [31 (22.6%)] including 17 Guillain-Barrè syndromes; (c) altered mental status [49 (35.8%)] including one necrotizing encephalitis and 2 cases with RT-PCR detection of SARS-Cov-2 RNA in CSF; (d) miscellaneous disorders, among whom 2 patients with myelopathy associated with Ab anti-SARS-CoV-2 in CSF. Patients with peripheral nervous system involvement had more frequently severe ARDS compared to patients with cerebrovascular disease (87.1% vs 42%; difference = 45.1% 95% CI 42.0-48.2; χ= 14.306; p < 0.0002) and with altered mental status (87.1% vs 55.6%; difference = 31.5% 95% CI 27.5-37.5%; χ= 7.055; p < 0.01).

Conclusion: This study confirms that involvement of nervous system is common in SARS-CoV-2 infection and offers clinicians useful information for prevention and prompt identification in order to set the adequate therapeutic strategies.
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http://dx.doi.org/10.1007/s00415-020-10251-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539268PMC
July 2021

Cladribine vs other drugs in MS: Merging randomized trial with real-life data.

Neurol Neuroimmunol Neuroinflamm 2020 11 14;7(6). Epub 2020 Aug 14.

From the Department of Health Sciences (A. Signori, M.P.S.), Section of Biostatistics, University of Genoa; Department of Neurosciences (F.S., R.L., C.V.R.), Reproductive Sciences and Odontostomatology, Multiple Sclerosis Center, Federico II University, Naples; Neurological Clinic and Multiple Sclerosis Center of "AORN A.Cardarelli" (G.T.M.), Naples; Centro di Sclerosi Multipla (E.S.), II Clinica Neurologica, Università della Campania "Luigi Vanvitelli," Napoli; 2nd Neurology Unit and CRRSM (Regional Referral Multiple Sclerosis Center) (A.M.R.), Careggi University Hospital, University of Florence; Multiple Sclerosis Study Center (P.A., D.B.), ASST Valle Olona, PO di Gallarate (VA); Clinical and Biological Sciences Department (M.C.), Neurology Unit, University of Torino, San Luigi Gonzaga Hospital, Orbassano; Centro SM (E.B.), Dipartimento di Neuroscienze, Ospedale Universitario Città della Salute e della Scienza di Torino; Neurological Clinic (R.C.), Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona; Policlinic Tor Vergata (G.M., D.L.), Rome; The Multiple Sclerosis Center of the Veneto Region (P.P.), Department of Neurosciences, University of Padua; Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences (S. Bonavita, L.L., S.E., D.I.), University of Campania Luigi Vanvitelli, Naples; Department of Clinical and Experimental Medicine (I.R.Z.), University of Sassari; Department Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (A.L.), Center of Excellence for Biomedical Research (CEBR), University of Genova; Neuroimmunology and Neuromuscular Diseases Unit (L.P.-G., V.T.C.), IRCCS Foundation Carlo Besta Neurological Institute, Milan; Centro Sclerosi Multipla ASST Papa Giovanni XXIII di Bergamo (S.L.G., B.F., V.B.); Department of Medical Science and Public Health (J.F., E.C., G.F.), University of Cagliari; Neurology Clinic (A. Sartori), Department of Medical, Surgical, and Health Sciences, University of Trieste; Multiple Sclerosis Center (S.R., C.C.), ASST Spedali Civili, PO di Montichiari (BS); Department of Medicine, Surgery and Neuroscience (M.L.S.), University of Siena; 2nd Neurology Unit and CReSM (Regional Referral Multiple Sclerosis Center) (A.D.S.), AOU San Luigi Gonzaga, Orbassano, Torino; Regina Montis Regalis Hospital (A.D.S.), Mondovì; Department of Neurology and Psychiatry (S.P.), Sapienza University, Rome; Neurologia Universitaria OORR (R.G.), Foggia; Institute of Neurology (S. Barone), University Magna Graecia of Catanzaro; Department of Neurology (C.B.), Valduce Hospital, Como; Merck Serono S.p.A. (A.V.), Rome; and IRCCS Ospedale Policlinico San Martino (A.L., M.P.S.), Genova, Italy.

Objective: Cladribine tablets were tested against placebo in randomized controlled trials (RCTs). In this study, the effectiveness of cladribine vs other approved drugs in patients with relapsing-remitting MS (RRMS) was compared by matching RCT to observational data.

Methods: Data from the pivotal trial assessing cladribine tablets vs placebo (CLARITY) were propensity score matched to data from the Italian multicenter database i-MuST. This database included 3,150 patients diagnosed between 2010 and 2018 at 24 Italian MS centers who started a disease-modifying drug. The annualized relapse rate (ARR) over 2 years from treatment start and the 24-week confirmed disability progression were compared between patients treated with cladribine and other approved drugs (interferon, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate), with comparisons with placebo as a reference. Treatment effects were estimated by the inverse probability weighting negative binomial regression model for ARR and Cox model for disability progression. The treatment effect has also been evaluated according to baseline disease activity.

Results: All weighted baseline characteristics were well balanced between groups. All drugs tested had an effect vs placebo close to that detected in the RCT. Patients treated with cladribine had a significantly lower ARR compared with interferon (relapse ratio [RR] = 0.48; < 0.001), glatiramer acetate (RR = 0.49; < 0.001), and dimethyl fumarate (RR = 0.6; = 0.001); a similar ARR to that with fingolimod (RR = 0.74; = 0.24); and a significantly higher ARR than natalizumab (RR = 2.13; = 0.014), confirming results obtained by indirect treatment comparisons from RCTs (network meta-analyses). The relative effect of cladribine tablets 10 mg (cumulative dose 3.5 mg/kg over 2 years) was higher in patients with high disease activity vs all treatments except fingolimod and natalizumab. Effects on disability progression were largely nonsignificant, probably due to lack of power for such analysis.

Conclusion: In patients with RRMS, cladribine tablets showed lower ARR compared with matched patients who started interferon, glatiramer acetate, or dimethyl fumarate; was similar to fingolimod; and was higher than natalizumab. The beneficial effect of cladribine tablets was generally amplified in the subgroup of patients with high disease activity.

Classification Of Evidence: This study provides Class III evidence that for patients with RRMS, cladribine-treated patients had lower ARR compared with interferon, glatiramer acetate, or dimethyl fumarate; similar ARR compared with fingolimod; and higher ARR compared with natalizumab.
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http://dx.doi.org/10.1212/NXI.0000000000000878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641098PMC
November 2020

First therapy choice in newly diagnosed Multiple Sclerosis patients: A multicenter Italian study.

Mult Scler Relat Disord 2020 Jul 16;42:102059. Epub 2020 Mar 16.

Department of Neurology, Valduce Hospital, Como.

Background: The approval of an increasing number of disease modifying drugs for the treatment of Multiple Sclerosis (MS) creates new challenges for patients and clinicians on the first treatment choice. The main aim of this study was to assess factors impacting first therapy choice in a large Italian MS cohort.

Methods: Newly diagnosed relapsing-remitting (RR) MS patients (2010-2018) followed in 24 Italian MS centres were included in the study. We evaluated the association of baseline demographics, clinical and MRI characteristics to the first treatment choice by logistic regression models applied to pre-defined binary alternatives: dimethyl fumarate vs injectables (interferon and glatiramer acetate), teriflunomide vs injectables, fingolimod vs dimethyl fumarate and fingolimod vs natalizumab.

Results: We enrolled 3025 patients in the period between January 2010 and June 2018. Relapses in the previous year (OR = 2.75; p = 0.001), presence of spinal cord lesions (OR = 1.80; p = 0.002) and higher number (>9) of T2 lesions on the baseline brain MRI scan (OR = 1.65; p = 0.022) were the factors associated to dimethyl fumarate choice as first therapy vs an injectable drug. Older age (OR = 1.06; p < 0.001), male sex (OR = 2.29; p = 0.001) and higher EDSS (OR = 1.36; p < 0.001) were the factors associated with the choice of teriflunomide vs injectables. In more recent years, dimethyl fumarate (OR = 3.23; p < 0.001) and teriflunomide (OR = 2.53; p < 0.001) were chosen more frequently than injectables therapies. The main determinant for the choice of fingolimod as compared with dimethyl fumarate was a higher EDSS (OR = 1.56; p = 0.001), while there was a weak association with a longer disease duration (p = 0.068) and a longer time from onset to diagnosis (p = 0.085). Compared to fingolimod, natalizumab was preferred in patients with a younger age (OR = 0.95; p = 0.003) and higher EDSS (OR = 1.45; p = 0.007) and a shorter disease duration (OR = 0.52; p = 0.076).

Conclusion: Many factors guided therapeutic decision for our Italian cohort of MS patients; they are mainly related to MS disease activity, baseline EDSS, disease duration and age.
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http://dx.doi.org/10.1016/j.msard.2020.102059DOI Listing
July 2020

Outcomes after fingolimod to alemtuzumab treatment shift in relapsing-remitting MS patients: a multicentre cohort study.

J Neurol 2019 Oct 17;266(10):2440-2446. Epub 2019 Jun 17.

Department of Medical Sciences and Public Health, Multiple Sclerosis Centre, University of Cagliari-ATS Sardegna, Via Is Guadazzonis 2, 09126, Cagliari, Italy.

Background: A high reactivation of multiple sclerosis (MS) was reported in patients treated with alemtuzumab after fingolimod. We aimed to understand whether this shift enhanced the risk for reactivation in a real-life cohort.

Methods: Subjects with relapsing MS, shifting from fingolimod to alemtuzumab were enrolled. We collected the following data: age, sex, disease duration, relapses after fingolimod withdrawal, new T2/gadolinium (Gd)-enhancing lesions in the last magnetic resonance imaging (MRI) during fingolimod and in the first, while on alemtuzumab, lymphocyte counts at alemtuzumab start, and Expanded Disability Status Scale (EDSS) before and after alemtuzumab.

Results: We enrolled 77 patients (women 61 (79%); mean age 36.2 years (SD 9.6), and disease duration 12.3 years (SD 6.8) at fingolimod discontinuation; median washout 1.8 months). The annualised relapse rate was 0.89 during fingolimod, 1.32 during washout, and 0.15 after alemtuzumab (p = 0.001). The EDSS changed from a median of 3 (IQR 2-4) at the end of fingolimod to 2.5 after alemtuzumab (IQR 1.5-4) (p = 0.013). The washout length and the lymphocyte count before alemtuzumab were not associated with EDSS change after alemtuzumab (p = 0.59 and p = 0.33, respectively). MRI activity decreased after alemtuzumab compared to that during fingolimod (p = 0.001). At alemtuzumab start, lymphocyte counts were < 0.8 × 10/mL in 21 patients.

Conclusions: In our cohort, alemtuzumab reduced relapse, new T2/Gd-enhancing lesions, and EDSS score, as compared to the previous periods (fingolimod/washout). These results were not related to washout length or lymphocyte counts. Therefore, a rapid initiation of alemtuzumab after fingolimod does not seem to be a risk factor for MS reactivation.
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http://dx.doi.org/10.1007/s00415-019-09424-8DOI Listing
October 2019

Determinants of therapy switch in multiple sclerosis treatment-naïve patients: A real-life study.

Mult Scler 2019 08 25;25(9):1263-1272. Epub 2018 Jul 25.

2nd Neurology Unit and CRRSM (Regional Referral Multiple Sclerosis Center), AOU San Luigi Gonzaga, Torino, Italy; Regina Montis Regalis Hospital, Mondovì, Italy.

Background: With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences.

Objectives: To identify prognostic factors for early switch after first therapy choice.

Methods: Newly diagnosed relapsing-remitting MS patients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models.

Results: We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50;  = 0.009), natalizumab (HR = 0.13;  < 0.001), dimethyl-fumarate (HR = 0.60;  = 0.037), teriflunomide (HR = 0.21;  = 0.031) as compared to interferons. Younger age (HR = 0.96;  < 0.001), diagnosis delay (HR = 1.23;  = 0.021), higher baseline Expanded Disability Status Scale (HR = 1.17;  = 0.001), and spinal cord lesions (HR = 1.46;  = 0.001) were independently associated with higher inefficacy switch rates. We found lower switch for intolerance/safety with glatiramer acetate (HR = 0.61;  = 0.001), fingolimod (HR = 0.35;  = 0.002), and dimethyl-fumarate (HR = 0.57;  = 0.022) as compared to interferons, while it increased with natalizumab (HR = 1.43;  = 0.022). Comorbidities were associated with intolerance switch (HR = 1.28;  = 0.047).

Conclusion: Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.
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http://dx.doi.org/10.1177/1352458518790390DOI Listing
August 2019

Assessing association of comorbidities with treatment choice and persistence in MS: A real-life multicenter study.

Neurology 2017 Nov 1;89(22):2222-2229. Epub 2017 Nov 1.

Objective: To assess whether the presence of concomitant diseases at multiple sclerosis (MS) diagnosis is associated with the choice and the treatment persistence in an Italian MS cohort.

Methods: We included newly diagnosed patients (2010-2016) followed in 20 MS centers and collected demographic and clinical data. We evaluated baseline factors related to the presence of comorbidities and the association between comorbidities and the clinical course of MS and the time to the first treatment switch.

Results: The study cohort included 2,076 patients. Data on comorbidities were available for 1,877/2,076 patients (90.4%). A total of 449/1,877 (23.9%) patients had at least 1 comorbidity at MS diagnosis. Age at diagnosis (odds ratio 1.05, 95% confidence interval [CI] 1.04-1.06; < 0.001) was the only baseline factor independently related to the presence of comorbidities. Comorbidities were not significantly associated with the choice of the first disease-modifying treatment, but were significantly associated with higher risk to switch from the first treatment due to intolerance (hazard ratio 1.42, CI 1.07-1.87; = 0.014). Association of comorbidities with risk of switching for intolerance was significantly heterogeneous among treatments (interferon β, glatiramer acetate, natalizumab, or fingolimod; interaction test, = 0.04).

Conclusions: Comorbidities at diagnosis should be taken into account at the first treatment choice because they are associated with lower persistence on treatment.
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http://dx.doi.org/10.1212/WNL.0000000000004686DOI Listing
November 2017

Pathophysiology, assessment and management of multiple sclerosis fatigue: an update.

Expert Rev Neurother 2017 04 21;17(4):373-379. Epub 2016 Oct 21.

a USC Neurologia , ASST Papa Giovanni XXIII , Bergamo , Italy.

Introduction: Fatigue is one of the most common symptoms associated with multiple sclerosis, affecting almost 80% of patients with 55% of them reporting it as one of the worst symptoms experienced, often independently of the level of disability. Areas covered: We review the main pathophysiological hypothesis, fatigue assessment scales, and its management. Expert commentary: Fatigue pathophysiology is complex and is often influenced by other secondary but relevant factors (e.g. psychological disturbances, musculoskeletal problems, sleep disorders and medication side effects) which may vary over time. Both peripheral and central mechanisms are implicated. The large heterogeneity of the assessment scales, which were used in the therapeutic trials, is partially responsible for the uncertainty of their results. To date, the best therapeutic approach seems to be from a multidisciplinary management involving exercise, rehabilitation and education in conjunction with medication.
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http://dx.doi.org/10.1080/14737175.2017.1247695DOI Listing
April 2017

Erythroblastaemia in natalizumab-treated patients with multiple sclerosis.

Mult Scler Relat Disord 2016 Jul 2;8:141-4. Epub 2016 Jun 2.

Clinical Chemistry Laboratory, Hospital Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy. Electronic address:

Background: Natalizumab is a monoclonal antibody that significantly reduces the occurrence of relapses in relapse-remitting multiple sclerosis (RRMS) patients. Early papers on the clinical use of natalizumab in RRMS patients reported erythroblastemia as occasional and transient.

Objectives: to determine the prevalence and absolute count of erythroblasts (nucleated red blood cells, NRBCs) in peripheral blood of RRMS patients in different treatment groups and healthy controls from the same geographic area using the same equipment for laboratory analysis.

Methods: We retrospectively evaluated the samples of 203 consecutive RRMS patients including 26 subjects on natalizumab, 17 on fingolimod, 72 on interferon, 41 on glatiramer acetate, 47 treatment-naïve and 240 healthy controls from the same geographic area. Blood samples were processed using an XN-9000-Hematology Analyzer and subsequent microscopic verification. In the natalizumab-treated patients we performed an additional analysis in order to detect the expression of CD34+ cells in peripheral blood, as confirmation of a bone marrow mobilization.

Results: The prevalence of patients with NRBCs positivity was significantly higher in natalizumab-treated patients (92%) compared with the other treatment groups and healthy controls (0%) (p<0.0005). The median absolute NRBCs count was significantly higher in natalizumab-treated patients (median 0.020, p<0.0005) than in the other treatment groups and healthy controls. Natalizumab-treated patients also had higher levels of white blood cells than all other groups and lower haemoglobin levels than healthy subjects (p<0.01), but no morphologic alterations were evident at a subsequent review of red blood cells, platelets and white blood cells. CD34+ cells levels were consistent with mobilization of haematopoietic stem cells from the bone marrow (median 8 cells/µL, IQR 5-12).

Conclusions: We confirm erythroblastaemia as a frequent finding of natalizumab treatment in RRMS patients. More extended knowledge and adequate long-term observation of this phenomenon are essential to better understand any pathological implication.
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http://dx.doi.org/10.1016/j.msard.2016.05.020DOI Listing
July 2016

Glatiramer acetate-induced hepatitis in a young female patient with multiple sclerosis.

Mult Scler Relat Disord 2014 Nov 15;3(6):732-4. Epub 2014 Aug 15.

Department of Neuroscience, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.

We report the first Italian case of glatiramer acetate-related acute hepatotoxicity. A 25-years-old woman suffering from multiple sclerosis presented acute hepatitis after eight months of treatment. Neither infective, nor autoimmune markers were detected. Liver biopsy histology was consistent with drug-induced acute injury. Liver function tests became normal after eight weeks of treatment discontinuation. This report points out the importance of monitoring liver function during the first year of treatment with glatiramer acetate.
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http://dx.doi.org/10.1016/j.msard.2014.08.001DOI Listing
November 2014

Defining minor symptoms in acute ischemic stroke.

Cerebrovasc Dis 2015 14;39(3-4):209-15. Epub 2015 Mar 14.

San Raffaele Scientific Institute-Institute of Experimental Neurology, Stroke Unit-Department of Neurology and Neurophysiology, Milan, Italy.

Background: Thrombolysis is often withheld from acute ischemic stroke patients presenting with mild symptoms; however, up to 40% of these patients end up with a poor outcome when left untreated. Since there is lack of consensus on the definition of minor symptoms, we aimed at addressing this issue by looking for features that would better predict functional outcomes at 3 months.

Methods: Among all acute ischemic stroke patients admitted to our Stroke Unit (n = 1,229), we selected a cohort of patients who arrived within 24 hours from symptoms onset, with baseline NIHSS ≤6, not treated with thrombolysis (n = 304). Epidemiological data, comorbidities, radiological features and clinical presentation (NIHSS items) were collected to identify predictors of outcome. Our cohort was tested against minor stroke definitions selected from the literature and a newly proposed one.

Results: Three months after stroke onset, 97 patients (31.9%) had mRS ≥ 2. Independent predictors of poor outcome were age (OR 0.97 [95% CI 0.95-9.99]) and baseline NIHSS score (OR 0.79 [95% CI 0.67-0.94]), while cardioembolic aetiology was negatively associated (OR 3.29 [95% CI 1.51-7.14]). Items of NIHSS associated with poor outcome were impairment of right motor arm (OR 0.49 [95% CI 0.27-0.91]) or the involvement of any of the motor items (OR 0.69 [95% CI 0.48-0.99]). The definition of minor stroke as NIHSS ≤3 and the new proposed definition had the highest sensitivity and accuracy and were independent predictors of outcome.

Conclusions: Our study confirmed that in spite of a low NIHSS score, one third of patients had poor outcome. As already described, age and NIHSS score remained independent predictors of poor outcome even in mild stroke. Also, motor impairment appeared a major determinant of poor outcome. The new proposed definition of minor stroke featured the NIHSS score and the NIHSS items that better predicted functional outcome. Awareness that even minor stroke can yield to poor outcome should sensitize patients to arrive early to the ED and neurologists to administer rt-PA.
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http://dx.doi.org/10.1159/000375151DOI Listing
February 2016

Wake-up stroke within 3 hours of symptom awareness: imaging and clinical features compared to standard recombinant tissue plasminogen activator treated stroke.

J Stroke Cerebrovasc Dis 2013 Aug 30;22(6):703-8. Epub 2011 Nov 30.

Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.

Background: Patients with wake-up stroke (WUS) are excluded from thrombolysis because of unknown time of symptom onset. Previous studies have reported similar stroke severity and early ischemic changes (EICs) in patients with WUS and stroke of known onset. These studies, however, included patients within a large timeframe to imaging or did not quantify EICs. The aim of our study was to quantify EICs of patients with WUS presenting within 3 hours of symptom recognition compared to standard 3-hours recombinant tissue plasminogen activator (rt-PA)-treated patients and assess the extent of ischemic lesion and functional independence at follow-up.

Methods: Patients were selected from our prospectively collected stroke database. Baseline and follow-up computed tomographic scans were graded with Alberta Stroke Program Early Computed Tomography Score (ASPECTS). Clinical outcome measures were modified Rankin Scale score, mortality, and symptomatic intracerebral hemorrhage.

Results: Demographic features, risk factors, stroke severity, and baseline ASPECTS were similar in both groups. WUS and rt-PA-treated patients had similar tissue outcome (median ASPECTS 7.0 vs 7.5; P = .202). Functional outcome was more favorable in rt-PA-treated patients (61.6% vs 43.1%; odds ratio [OR] 2.12; 95% confidence interval [CI] 1.05-4.28; P = .037). After adjusting for age, stroke severity, treatment, and EICs in less than one-third of middle cerebral artery territory, rt-PA and National Institutes of Health Stroke Scale scores remained the only significant predictors of outcome (OR 7.76; 95% CI 2.40-25.05; P = .001 and OR 0.74; 95% CI 0.67-0.82; P < .001, respectively).

Conclusions: Within 3 hours of symptom recognition, patients with WUS have EICs similar to rt-PA-treated patients. It is reasonable to expect that selected WUS patients might benefit from thrombolysis within 3 hours of symptom awareness.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2011.10.003DOI Listing
August 2013
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