Since coronavirus disease-2019 (COVID-19) outbreak in January 2020, several pieces of evidence suggested an association between the spectrum of Guillain–Barré syndrome (GBS) and severe acute ...respiratory syndrome coronavirus-2 (SARS-CoV-2). Most findings were reported in the form of case reports or case series, whereas a comprehensive overview is still lacking. We conducted a systematic review and searched for all published cases until July 20th 2020. We included 73 patients reported in 52 publications. A broad age range was affected (mean 55, min 11–max 94 years) with male predominance (68.5%). Most patients showed respiratory and/or systemic symptoms, and developed GBS manifestations after COVID-19. However, asymptomatic cases for COVID-19 were also described. The distributions of clinical variants and electrophysiological subtypes resemble those of classic GBS, with a higher prevalence of the classic sensorimotor form and the acute inflammatory demyelinating polyneuropathy, although rare variants like Miller Fisher syndrome were also reported. Cerebrospinal fluid (CSF) albuminocytological dissociation was present in around 71% cases, and CSF SARS-CoV-2 RNA was absent in all tested cases. More than 70% of patients showed a good prognosis, mostly after treatment with intravenous immunoglobulin. Patients with less favorable outcome were associated with a significantly older age in accordance with previous findings regarding both classic GBS and COVID-19. COVID-19-associated GBS seems to share most features of classic post-infectious GBS and possibly the same immune-mediated pathogenetic mechanisms. Nevertheless, more extensive epidemiological studies are needed to clarify these issues.
Background
Dysautonomic symptoms (DS) are frequent but often underrecognized in multiple sclerosis (MS) patients, despite the relevant impact on quality of life and physical performance.
Objectives
...To assess frequency and characteristics of DS in our MS population compared with healthy controls (HC). To investigate the relationship between DS and disease characteristics (MS subtype, disease duration, Expanded Disability Status Scale (EDSS), clinical and/or radiological activity, disability progression).
Patients and methods
Cross-sectional study includes 324 MS patients (mean age 44.9 ± 10.7 years; 66% female) and 190 HC (mean age 40.60 ± 12.83 years; 63% female). DS were assessed using the Italian validated version of the Composite Autonomic Symptom Score-31 (COMPASS-31). Possible confounding factors were considered.
Results
More than 94% of enrolled MS patients reported alterations in ≥ 2 domains of the COMPASS-31 scale (score > 0) and significantly higher COMPASS-31 total and single domain median scores compared with HC, independently from possible confounding factors (orthostatic intolerance:
p
= 0.001; vasomotor:
p
= 0.017; secretomotor:
p
= 0.040; gastrointestinal:
p
= 0.047; bladder:
p
< 0.001; pupillomotor:
p
< 0.001; COMPASS-31 total score:
p
< 0.001). COMPASS-31 total, secretomotor, gastrointestinal, and bladder domain scores showed weak to moderate correlation with disease duration (Rho = 0.19,
p
< 0.001; Rho = 0.18,
p
= 0.01; Rho = 0.25,
p
= 0.030; Rho = 0.28,
p
< 0.001, respectively). A moderate correlation between EDSS score, COMPASS-31 total, and bladder domain scores (Rho = 0.32,
p
< 0.001 and Rho = 0.48,
p
< 0.001, respectively) was observed. Progressive subtypes showed higher COMPASS-31 total (
p
= 0.025), gastrointestinal (
p
= 0.07), and bladder (
p
< 0.001) domain scores vs relapsing-remitting patients.
Conclusions
Our findings confirm that MS-related DS are frequent and tend to increase paralleling disease duration and clinical worsening, reaching the highest clinical impact in progressive subtypes.
Multiple sclerosis (MS) primarily affects adult females. However, in the last decades, rising incidence and prevalence have been observed for demographic extremes, such as pediatric-onset MS (POMS; ...occurring before 18 years of age) and late-onset MS (corresponding to an onset above 50 years). These categories show peculiar clinical-pathogenetic characteristics, aging processes and disease courses, therapeutic options, and unmet needs. Nonetheless, several open questions are still pending. POMS patients display an important contribution of multiple genetic and environmental factors such as EBV, while in LOMS, hormonal changes and pollution may represent disease triggers. In both categories, immunosenescence emerges as a pathogenic driver of the disease, particularly for LOMS. In both populations, patient and caregiver engagement are essential from the diagnosis communication to early treatment of disease-modifying therapy (DMTs), which in the elderly population appears more complex and less proven in terms of efficacy and safety. Digital technologies (e.g., exergames and e-training) have recently emerged with promising results, particularly in treating and following motor and cognitive deficits. However, this offer seems more feasible for POMS, being LOMS less familiar with digital technology. In this narrative review, we discuss how the aging process influences the pathogenesis, disease course, and therapeutic options of both POMS and LOMS. Finally, we evaluate the impact of new digital communication tools, which greatly interest the current and future management of POMS and LOMS patients.
We investigated incidence and outcome of spontaneous intracerebral hemorrhage (ICH) in a population-based stroke registry and provided data to inform on the figures of the disease in women and in ...men.
Our prospective population-based registry included patients with first-ever ICH occurring from January 2011 to December 2020. Incidence rates were standardized to the 2011 Italian and European population, and incidence rate ratios were calculated. Multivariate hazard ratios for 30-day and 1-year fatality were estimated with Cox regression, including components of the ICH score and sex. We included 748 first-ever ICHs (41.3% women). Women were significantly older than men at ICH onset (78.9±12.6 versus 73.2±13.6 years;
<0.001) and showed higher clinical severity on presentation (median National Institutes of Health Stroke Scale score, 11 interquartile range, 6-20 versus 9 interquartile range, 4-15, respectively;
=0.016). The crude annual incidence rate was 20.2 (95% CI, 18.0-22.6) per 100 000 person-years in women and 30.2 (95% CI, 27.4-33.2) per 100 000 person-years in men); incidence was lower in women versus men (incidence rate ratio, 0.67 95% CI, 0.58-0.78;
<0.001) and did not change over time in both sexes (
for trend=0.073 and 0.904, respectively). Unadjusted comparison showed higher 1-year case-fatality rates in women versus men (48.5% versus 40.1%;
=0.026). After adjusting for components of the ICH score, female sex lost significance as a predictor of mortality.
We found lower ICH incidence in women than in men. However, women showed a higher 1-year case-fatality rate versus men, which was likely related to older age at ICH onset and higher clinical severity. Identification of factors explaining the reported differences is important to develop targeted interventions.
Cladribine has been introduced as a high-efficacy drug for treating relapsing-remitting multiple sclerosis (RRMS). Initial cohort studies showed early disease activity in the first year after drug ...initiation. Biomarkers that can predict early disease activity are needed.
To estimate cerebrospinal fluid (CSF) markers of clinical and radiological responses after initiation of cladribine.
Forty-two RRMS patients (30F/12M) treated with cladribine were included in a longitudinal prospective study. All patients underwent a CSF examination at treatment initiation, clinical follow-up including Expanded Disability Status Scale (EDSS) assessment, and a 3T MRI scan after 6,12 and 24 months, including the evaluation of white matter (WM) and cortical lesions (CLs). CSF levels of 67 inflammatory markers were assessed with immune-assay multiplex techniques. The 'no evidence of disease activity' (NEDA-3) status was assessed after two years and defined by no relapses, no disability worsening measured by EDSS and no MRI activity, including CLs.
Three patients were lost at follow-up. At the end of follow-up, 19 (48%) patients remained free from disease activity. IFNgamma, Chitinase3like1, IL32, Osteopontin, IL12(p40), IL34, IL28A, sTNFR2, IL20 and CCL2 showed the best association with disease activity. When added in a multivariate regression model including age, sex, and baseline EDSS, Chitinase 3 like1 (p = 0.049) significantly increased in those patients with disease activity. Finally, ROC analysis with Chitinase3like1 added to a model with EDSS, sex, age previous relapses, WM lesion number, CLs, number of Gad enhancing lesions and spinal cord lesions provided an AUC of 0.76 (95%CI 0.60-0.91).
CSF Chitinase 3 like1 might provide prognostic information for predicting disease activity in the first years after initiation of cladribine. The drug's effect on chronic macrophage and microglia activation deserves further evaluation.
IntroductionFast and accurate diagnosis of acute stroke is crucial to timely initiate reperfusion therapies. Conventional high-field (HF) MRI yields the highest accuracy in discriminating early ...ischaemia from haemorrhages and mimics. Rapid access to HF-MRI is often limited by contraindications or unavailability. Low-field (LF) MRI (<0.5T) can detect several types of brain injury, including ischaemic and haemorrhagic stroke. Implementing LF-MRI in acute stroke care may offer several advantages, including extended applicability, increased safety, faster administration, reduced staffing and costs. This multicentric prospective open-label trial aims to evaluate the diagnostic accuracy of LF-MRI, as a tool to guide treatment decision in acute stroke.Methods and analysisConsecutive patients accessing the emergency department with suspected stroke dispatch will be recruited at three Italian study units: Azienda Sanitaria Locale (ASL) Abruzzo 1 and 2, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital. The estimated sample size is 300 patients. Anonymised clinical and LF-MRI data, along with conventional neuroimaging data, will be independently assessed by two external units: Marche Polytechnic University and ‘G. Martino’ Polyclinic University Hospital. Both units will independently adjudicate the best treatment option, while the latter will provide historical HF-MRI data to develop artificial intelligence algorithms for LF-MRI images interpretation (Free University of Bozen-Bolzano). Agreement with conventional neuroimaging will be evaluated at different time points: hyperacute, acute (24 hours), subacute (72 hours), at discharge and chronic (4 weeks). Further investigations will include feasibility study to develop a mobile stroke unit equipped with LF-MRI and cost-effectiveness analysis. This trial will provide necessary data to validate the use of LF-MRI in acute stroke care.Ethics and disseminationThe study was approved by the Research Ethics Committee of the Abruzzo Region (CEtRA) on 11 May 2023 (approval code: richyvgrg). Results will be disseminated in peer-reviewed journals and presented in academic conferences.Trial registration numberNCT05816213; Pre-Results.
Background and aims Fast-track care have been proved to reduce the short-term risk of stroke after transient ischemic attack (TIA). We aimed to investigate stroke risk and to characterize short- and ...long-term stroke predictors in a large cohort of TIA patients undergoing fast-track management. Methods Prospective study, enrolling consecutive TIA patients admitted to a Northern Italy emergency department from August 2010 to December 2017. All patients underwent fast-track care within 24 h of admission. The primary outcome was defined as the first stroke recurrence at 90 days, 12 and 60 months after TIA. Stroke incidence with 95% confidence interval (CI) at each timepoint was calculated using Poisson regression. Predictors of stroke recurrence were evaluated with Cox regression analysis. The number needed to treat (NNT) of fast-track care in preventing 90-day stroke recurrence in respect to the estimates based on baseline ABCD 2 score was also calculated. Results We enrolled 1,035 patients (54.2% males). Stroke incidence was low throughout the follow-up with rates of 2.2% 95% CI 1.4–3.3% at 90 days, 2.9% 95% CI 1.9–4.2% at 12 months and 7.1% 95% CI 5.4–9.0% at 60 months. Multiple TIA, speech disturbances and presence of ischemic lesion at neuroimaging predicted stroke recurrence at each timepoint. Male sex and increasing age predicted 90-day and 60-month stroke risk, respectively. Hypertension was associated with higher 12-month and 60-month stroke risk. No specific TIA etiology predicted higher stroke risk throughout the follow-up. The NNT for fast-track care in preventing 90-day stroke was 14.5 95% CI 11.3–20.4 in the overall cohort and 6.8 95% CI 4.6–13.5 in patients with baseline ABCD 2 of 6 to 7. Conclusion Our findings support the effectiveness of fast-track care in preventing both short- and long-term stroke recurrence after TIA. Particular effort should be made to identify and monitor patients with baseline predictors of higher stroke risk, which may vary according to follow-up duration.
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