Long-term follow-up (up to 11 years) of an Italian pediatric MS cohort treated with Natalizumab: a multicenter, observational study.

BACKGROUND: Natalizumab (NAT) has a strong impact on disease activity of aggressive pediatric multiple sclerosis (MS), with no difference in safety profile compared to adult MS. However, available data are limited by short follow-up. Our aim was to report long-term follow-up data (up to 11 years) of a large Italian pediatric MS cohort treated with NAT. MATERIALS AND METHODS: We retrospectively collected data of pediatric MS patients treated with NAT included in a previous study and prospectively followed in Italian MS centers. We compared disease activity pre, during, and post-NAT and we performed survival analyses of time to evidence of disease activity (EDA) during NAT, time to reach EDA post-NAT, and time to NAT discontinuation. RESULTS: Ninety-two patients were included from 19 MS centers in Italy. At NAT initiation, cohort's characteristics were as follows: 55 females; 14.7 ± 2.4 (mean ± SD) years of age; 34 naïve to disease modifying therapies; 1-year pre-NAT annualized relapse rate (ARR): 2.2 ± 1.2; EDSS (median [IQR]): 2.5 [2.0-3.0]; gadolinium-enhancing lesions: 2 [1-5]; 41 JCV positives. During NAT treatment (61.9 ± 35.2 mean infusions), ARR lowered to 0.08 ± 0.23 (p < 0.001), EDSS score to 1.5 [1.0-2.5] at last infusion (p < 0.001), and 51% patients had EDA (21% after 6 months of rebaseline). No serious adverse events were reported. Forty-nine patients discontinued NAT, mainly due to PML concern; the majority (29/49) had disease reactivation in the subsequent 12 months, of which three with a clinical rebound. CONCLUSION: NAT treatment maintains its high efficacy for a long time in pediatric MS patients, with no new safety issues.

Facial and bodily emotion recognition in multiple sclerosis: the role of alexithymia and other characteristics of the disease.

Multiple sclerosis (MS) may be associated with impaired perception of facial emotions. However, emotion recognition mediated by bodily postures has never been examined in these patients. Moreover, several studies have suggested a relation between emotion recognition impairments and alexithymia. This is in line with the idea that the ability to recognize emotions requires the individuals to be able to understand their own emotions. Despite a deficit in emotion recognition has been observed in MS patients, the association between impaired emotion recognition and alexithymia has received little attention. The aim of this study was, first, to investigate MS patient's abilities to recognize emotions mediated by both facial and bodily expressions and, second, to examine whether any observed deficits in emotions recognition could be explained by the presence of alexithymia. Thirty patients with MS and 30 healthy matched controls performed experimental tasks assessing emotion discrimination and recognition of facial expressions and bodily postures. Moreover, they completed questionnaires evaluating alexithymia, depression, and fatigue. First, facial emotion recognition and, to a lesser extent, bodily emotion recognition can be impaired in MS patients. In particular, patients with higher disability showed an impairment in emotion recognition compared with patients with lower disability and controls. Second, their deficit in emotion recognition was not predicted by alexithymia. Instead, the disease's characteristics and the performance on some cognitive tasks significantly correlated with emotion recognition. Impaired facial emotion recognition is a cognitive signature of MS that is not dependent on alexithymia.

Evaluation of drivers of treatment switch in relapsing multiple sclerosis: a study from the Italian MS Registry.

BACKGROUND: Active relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) are currently defined as "relapsing MS" (RMS). The aim of this cross-sectional study was to assess drivers of treatment switches due to clinical relapses in a population of RMS patients collected in the Italian MS and Related Disorders Register (I-MS&RD). METHODS: RRMS and SPMS patients with at least one relapse in a time window of 2 years before of data extraction were defined as RMS. Factors associated with disease-modifying therapy (DMT) switching due to clinical activity were assessed through multivariable logistic regression models in which treatment exposure was included as the last recorded DMT and the last DMT's class [moderate-efficacy (ME), high-efficacy (HE) DMTs and anti-CD20 drugs]. RESULTS: A cohort of 4739 RMS patients (4161 RRMS, 578 SPMS) was extracted from the I-MS&RD. A total of 2694 patients switching DMTs due to relapses were identified. Switchers were significantly (p < 0.0001) younger, less disabled, more frequently affected by an RR disease course in comparison to non-switcher patients. The multivariable logistic regression models showed that Alemtuzumab (OR 0.08, 95% CI 0.02-0.37), Natalizumab (0.48, 0.30-0.76), Ocrelizumab (0.1, 0.02-0.45) and Rituximab (0.23, 0.06-0.82) exposure was a protective factor against treatment switch due to relapses. Moreover, the use of HE DMTs (0.43, 0.31-0.59), especially anti-CD20 drugs (0.14, 0.05-0.37), resulted to be a protective factor against treatment switch due to relapses in comparison with ME DMTs. CONCLUSIONS: More than 50% of RMS switched therapy due to disease activity. HE DMTs, especially anti-CD20 drugs, significantly reduce the risk of treatment switch.

Delirium prevalence, risk factors and outcomes among patients with acute stroke: A multi-centre observational study.

BACKGROUND: Delirium is a frequent and serious acute neuropsychiatric syndrome leading to worse prognosis including mortality. Patients with ischaemic and/or haemorrhagic stroke are vulnerable to delirium. However, predisposing and precipitating factors have not been fully discovered to date, leaving this area of practice under-represented in available guidelines. AIMS: To describe the prevalence, associated factors and main in-hospital outcomes of post-stroke delirium. METHODS: A multi-centre observational study was conducted from 2019 to 2020 and reported according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Data were collected in stroke units located in two large hospitals in the North-East region of Italy. Consecutive adult patients with ischaemic and/or haemorrhagic stroke with a Glasgow Coma Scale > 5, who were willing to participate, were included. Data at admission, during the in-hospital stay and at discharge were collected by trained nurses, not involved in the care of patients, with (a) validated tools, (b) direct observation, and (c) access of patients' records. RESULTS: A total of 78 patients were enrolled (mean 73.1 years; 59% male), and 70.5% of them had suffered an ischaemic stroke. The mean National Institutes of Health Stroke Scale (NIHSS) at admission was 8.2 ± 7.0. A total of 34.6% of patients developed post-stroke delirium; the onset was mainly on the first day of admission (70.4%) and the condition lasted for an average of 3.7 days (SD 2.6). In the multivariate logistic regression, 64.1% of the delirium variance was explained by the NIHSS scores (RR 1.259, 95%CI 1.035-1.533; p = 0.022). Patients with post-stroke delirium reported higher functional dependence at discharge and the need for more delaying of hospital care to be admitted in rehabilitation units. CONCLUSIONS: At admission, higher scores in the NIHSS evaluation might suggest which patients are at an increased risk of delirium. Avoiding interventions that could potentially increase this risk, together with continuous surveillance, become imperative for nurses who are constantly and closely present by their patients' side, in order to prevent this serious complication.

Lower lymphocyte counts and older age are associated with reduced multiple sclerosis disease activity during dimethyl fumarate treatment.

BACKGROUND: delayed-release dimethyl fumarate (DMF) is a disease modifying therapy for relapsing-remitting multiple sclerosis (MS) with antioxidant and anti-inflammatory properties. The drug causes lymphocyte count reduction, which can lead to lymphopenia development during treatment. This is an important safety issue, due to infectious risk, mainly progressive multifocal leukoencephalopathy (PML). If the lymphocyte count influences the response to treatment is still a matter of debate, as there are contrasting contrasting data in the literature. Considering this, we aimed to identify DMF induced lymphopenia risk factors and to evaluate lymphopenia impact on MS disease activity in a real world setting. METHODS: a retrospective study on 135 MS patients receiving DMF with a mean treatment duration of 32.3±15.9 months was performed. Baseline and follow-up demographic, clinical, magnetic resonance imaging (MRI) and laboratory data were collected. RESULTS: 44 patients (32.6%) developed lymphopenia, with 11 (8.1%) grade 1, 23 (17.0%) grade 2 and 10 (7.4 %) grade 3. Older age and lower basal absolute lymphocyte count were found to be associated with lymphopenia development on a binary regression model (p<0.001 and p=0.009). When compared with non lymphopenic+lymphopenia grade 1 patients, those experiencing lymphopenia grade 2+3 had longer disease activity free survival (p<0.001), fewer clinical relapses (p=0.005) and lower MRI disease activity (p≤0.001). On Cox regression model, older age and lymphopenia grade 2+3 were found to be protective factors against disease activity (HR=0.966; 95% C.I.=0.942-0.992; p=0.009 for age; HR=0.137; 95% C.I.=0.043-0.439; p=0.001 for lymphopenia grade 2+3) and MRI disease activity (HR=0.968; 95% C.I.=0.941-0.997; p=0.030 for age; HR=0.142; 95% C.I.=0.034-0.591; p=0.007 for lymphopenia grade 2+3). Only lymphopenia grade 2+3 was found to be a predictor of clinical relapses (HR=0.970; 95% C.I.=0.936-1.005; p=0.095 for age; HR=0.115; 95% C.I.=0.016-0.854; p=0.034 for lymphopenia grade 2+3), with a protective effect. CONCLUSION: older age and lower basal lymphocyte count were found to be associated with lymphopenia development. Lymphopenia grade 2+3 and older age could be protective against clinical and radiologic disease activity during DMF treatment.

Efficacy and Safety of Intravenous Thrombolysis in Patients with Acute Ischemic Stroke and Pre⁻Existing Disability.

Little is known about intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with pre-existing disability. Disabled patients are often excluded from IVT treatment. Previous studies investigated the role of pre-existing disability on outcomes in AIS patients after IVT. However, no studies have been conducted to date to determine whether IVT may improve clinical outcomes in AIS patients with pre-existing disability. The aim of our study was to evaluate efficacy and safety of IVT in patients with pre-existing moderate and moderately severe disability (pre-stroke modified Rankin Scale score = 3 or 4) affected by AIS. This study was based on a retrospective analysis of a prospectively collected database of consecutive patients admitted to the Udine University Hospital with AIS from January 2015 to May 2018. The efficacy endpoints were the rate of favorable outcome and rate of major neurological improvement. The safety endpoints were the rate of mortality at three months, presence of intracranial hemorrhage (ICH), and presence of symptomatic intracranial hemorrhage (sICH). The study population included 110 AIS patients with pre-existing moderate and moderately severe disability, 36 of which received (IVT+) and 74 did not receive IVT (IVT-). AIS disabled patients treated with IVT had higher rates of favorable outcome (66.7% vs. 36.5%, p = 0.003) and major neurological improvement (39.4% vs. 17.4%, p = 0.01) compared to non-treated ones. Two in three disabled patients returned to their pre-stroke functional status when treated with IVT. Prevalence of three-month mortality, ICH, and sICH did not differ in the two groups. Disabled patients affected by AIS significantly improved after IVT. Moderate and moderately severe disability alone should not be considered, per se, as a contraindication to IVT treatment.

Prior Use of Antiplatelet Therapy and Outcomes after Endovascular Therapy in Acute Ischemic Stroke Due to Large Vessel Occlusion: A Single-Center Experience.

Endovascular therapy (EVT) represents the gold standard treatment in patients affected by acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Prior antiplatelet (APT) therapy might increase the risk of bleeding and modify the clinical outcome of AIS patients treated with EVT. Thus, we compared effectiveness and safety of EVT in Caucasian patients with and without previous use of APT agents. We recruited consecutive patients admitted to Udine University Hospital with AIS undergoing EVT from January 2015 to December 2017. The following outcomes were documented: successful recanalization, 3-month favorable outcome, symptomatic intracranial hemorrhage (sICH), parenchymal hematoma (PH), and 3-month mortality. The study population included 100 patients (mean age 70.1 ± 11.2 years, 58% males). At time of admission, 34 patients were taking APT agents. Patients on APT pretreatment were older, had more vascular risk factors, and showed higher levels of serum creatinine than APT naïve patients. Moreover, prior APT therapy was associated with a higher rate of pre-stroke disability and a more severe stroke at admission. Patients pretreated with APT had higher rates of successful recanalization (91.2% vs. 74.2%, p = 0.04). Prevalence of 3-month unfavorable outcome and 3-month mortality was significantly higher in APT-pretreated patients than in those without APT pretreatment. However, these associations were not confirmed on multivariable analyses. Prevalence of sICH and PH did not differ in the two groups. APT pretreatment is associated to successful recanalization rate, without increasing the risk of intracranial bleeding in patients with LVO undergoing EVT.