Effect of patients' expectations on clinical response to fampridine treatment.

INTRODUCTION: Patient expectation of treatment outcome is one of the primary mechanisms underlying the placebo effect. In multiple sclerosis trials with symptomatic treatments, a robust placebo effect is observed, which might be related to patient expectations. The aim of this study was to evaluate whether patient expectations regarding fampridine treatment influence the clinical response after 4 weeks and 6 months of treatment. MATERIALS AND METHODS: We designed and carried out a prospective study from June 2015 to August 2017. Before treatment, patients completed a questionnaire including a scale evaluating their expectations regarding the treatment. The effect of baseline positive expectancy on the response status after 4 weeks and 6 months of treatment was analyzed through univariable and, when applicable, multivariable analysis. RESULTS: A total of 47 consecutive patients were included in the study. At week 4, 37 (78.7%) patients were classified as responders; a one-point increase in the positive expectancy questionnaire was significantly associated with a fourfold increase in the likelihood of being a responder [OR = 4.020 (95% CI 1.082-14.933); p = 0.038]. At 6 months, 43 patients completed follow-up. The number of responders decreased to 28; at this point, positive expectancy at baseline was no longer associated with response status. CONCLUSION: Baseline positive expectancy regarding fampridine was determinant of the clinical response after 4 weeks of treatment. However, in the long term, fampridine efficacy was not dependent on expectations prior to treatment.

The Influence of Menopause in Multiple Sclerosis Course: A Longitudinal Cohort Study.

BACKGROUND: Hormonal variations are known to influence the course of multiple sclerosis (MS). OBJECTIVES: We aimed to evaluate the impact of menopause in MS course, including disease activity and disability progression. METHODS: We conducted a retrospective longitudinal cohort study including all women, older than 44, post-menopausal, with a diagnosis of MS at least 1 year before menopause. We evaluated the impact of menopause in MS course comparing clinical and radiologic outcomes within 5 years before and after menopause. We repeated the analysis in subgroups of patients without disease-modifying treatment (DMT) change or co-morbidities diagnosed during the observation period, considering that those factors might also impact MS outcomes. RESULTS: Thirty-seven women, with a mean age at the time of menopause of 49.8 (±4.06) years were included in the analysis. Within 5 years following menopause, we observed a decrease in the annualized relapse rate (0.37 ± 0.35 pre-menopause vs. 0.08 ± 0.18 post-menopause, p < 0.001) compared with the same period before menopause, while the EDSS progression rate remained stable (0.13 ± 0.24 EDSS point/year pre-menopausal vs. 0.13 ± 0.18 post-menopause, p = 0.935). EDSS progression events frequency was similar before and after the menopause (37.8 vs. 48.6%, respectively, p = 0.424). These observations persisted in patients' subgroups without DMT switch or co-morbidities. CONCLUSIONS: Following menopause, we observed a reduction in the relapse rate, but the disability progression continued at a similar rate, compared to the pre-menopausal period. These observations persisted in the subgroup of patients without changes in DMT or co-morbidities diagnosed during the observation period.

Orolingual angiodema associated with alteplase treatment of acute stroke: a reappraisal.

BACKGROUND: Orolingual angioedema has been increasingly recognized as a potentially life-threatening complication associated with alteplase treatment of stroke. Concomitant treatment with an angiotension converting enzyme inhibitor (ACEi) and localization of infarction in the territory of middle cerebral artery seem to be associated with a higher risk of this complication. METHODS: We report the cases of orolingual angioedema among the patients undergoing alteplase treatment in our Stroke Unit. Additionally, we reviewed the literature to evaluate the pathophysiology, clinical characteristics, and treatment options. RESULTS: In our Stroke Unit, among 236 patients given alteplase for acute stroke, 8 patients (3.4%) developed angioedema. The clinical picture varied from localized labial edema to extensive lingual edema with respiratory distress but in all cases it gradually resolved with symptomatic treatment. Seven patients had a hemispheric stroke (4 with lateralized angioedema, contralateral to the ischemic lesion), whereas the other 1 patient had a right superior cerebellar artery stroke (with lateralized angioedema, ipsilateral to the ischemic lesion). The National Institutes of Health Stroke Scale score at admission ranged from 6 to 24 (median 12.5). Five patients were taking an ACEi. Our results are similar to previously published data. In the literature, it appears that orolingual angioedema occurs in .2-5.1% of all stroke patients receiving Alteplase treatment. CONCLUSIONS: Orolingual angioedema is a potential complication of which treating physicians in stroke units need to be aware, even in those cases without history of ACEi treatment and without infarction in the territory of the middle cerebral artery. All patients who receive alteplase treatment should be monitored carefully.

Spirito-Maron echocardiographic score: a marker for morphological and physiological assessment of patients with hypertrophic cardiomyopathy.

AIMS: The heterogeneous distribution of hypertrophy in hypertrophic cardiomyopathy (HCM) limits the echocardiographic conventional measurements accuracy in the evaluation of left ventricular hypertrophy (LVH). The aim of this study was to assess the correlation of the echocardiographic Spirito-Maron score (SMS) with left ventricle (LV) mass quantification by cardiac magnetic resonance (CMR) and with LV diastolic function. METHODS AND RESULTS: Left ventricle diastolic function parameters, SMS, LV mass (American Society of Echocardiography formula), and maximal wall thickness (MWT) were evaluated by two-dimensional (2D) transthoracic echocardiography. The SMS was obtained by adding the MWT of 4 LV segments, at the mitral valve or papillary muscles short-axis views. Echocardiographic parameters of LVH, including SMS, were correlated with LV mass obtained by CMR and with E/e' ratio. We included 45 patients (60% male, mean age 48 ± 18 years), who underwent 2D echocardiography. Twenty-two of them performed a CMR study. A positive correlation was found between SMS and CMR LV mass (r = 0.80; P < 0.001), whereas MWT (r = 0.62; P = 0.002) and the 2D LV mass (r = 0.60; P = 0.011) presented a lower correlation with CMR LV mass. The SMS was significantly correlated with E/e' ratio (r = 0.60; P = 0.007), whereas a nonsignificant correlation was found with MWT (r = 0.41; P = 0.081) and 2D LV mass (r = 0.22; P = 0.400). CONCLUSION: Spirito-Maron score presents a highly positive correlation with CMR LV mass and with diastolic dysfunction severity in HCM patients. SMS is a reliable quantitative LVH measurement method and seems to provide more comprehensive morphological and physiological information than 2D echocardiographic conventional parameters used to estimate LVH.

Nursing Ethical Decision Making on Adult Physical Restraint: A Scoping Review.

OBJECTIVE: to map the existing knowledge on nursing ethical decision making in the physical restraint of hospitalised adults. (1) Background: physical restraint is a technique that conditions the free movement of the body, with risks and benefits. The prevalence of physical restraint in healthcare suffers a wide variation, considering the environment or pathology, and it raises ethical issues that hinders decision making. This article intends to analyse and discuss this problem, starting from a literature review that will provoke a grounded discussion on the ethical and legal aspects. Inclusion criteria are: studies on physical restraint (C) and ethical nursing decision making (C) in hospitalized adults (P); (2) methods: a three-step search strategy was used according to the JBI. The databases consulted were CINAHL Plus with Full Text (EBSCOhost), MEDLINE Full Text (EBSCOhost), Nursing and Allied Health Collection: Comprehensive and Cochrane Database of Systematic Reviews (by Cochrane Library, RCAAP and Google Scholar. All articles were analysed by two independent reviewers; (3) results: according to the inclusion criteria, 18 articles were included. The categories that influence ethical decision in nursing are: consequence of the decision, the context, the nature of the decision in terms of its complexity, the principles of the ethical decision in nursing, ethical issues and universal values; (4) conclusions: the findings of this review provide evidence that there is extensive knowledge regarding nursing ethical decision making in adult physical restriction, also, it is considered an ethical issue with many associated assumptions. In this article we aim to confront all these issues from a legal perspective.

Discontinuation of disease-modifying therapy in MS patients over 60 years old and its impact on relapse rate and disease progression.

BACKGROUND / AIMS: The benefit of disease-modifying therapy (DMT) is unclear for older patients with multiple sclerosis (MS), namely those who have not experienced clinical disease activity for a prolonged time. We aimed to compare baseline differences and clinical outcomes between DMT discontinuers and continuers in a cohort of MS patients older than 60 years. METHODS: Retrospective, observational study identifying MS patients aged over 60 years, stable on DMT> 24 months. Additional inclusion criteria were a previous diagnosis of relapsing MS and a minimum follow-up period of 24 months. Differences between groups (continuers/discontinuers) were assessed. For risk of relapse and of confirmed disability worsening at follow up, a time to outcome survival model was constructed using Cox proportional hazards regression, testing for possible risk predictors. RESULTS: Thirty-five patients were included (68.6% female), with a mean age at diagnosis of 42.1 ( ± 9.5) years and a median EDSS score of 3 (IQR 2) at the age of 60 years (baseline). Thirteen patients discontinued DMT after baseline, in a mean follow-up time of 77.1 months ( ± 40.2). No differences were found between DMT continuers vs discontinuers. DMT discontinuation did not predict risk to relapse (HR 0.38, 95%CI 0.04-3.80, p = 0.408) or disability worsening at follow-up (HR 0.83, 95%CI 0.31-2.22, p = 0.712). MRI gadolinium-enhancing lesions and EDSS score > 3 at baseline were found to be independent predictors of risk to relapse and disability worsening at follow-up, respectively. CONCLUSION: DMT discontinuation did not seem to influence clinical outcome, equating with the perceived limited effect of continued immunomodulation on older stable and/or progressive patients.

Long-term survival, autonomy, and quality of life of elderly patients undergoing aortic valve replacement.

AIMS: We reviewed the long-term survival, autonomy, and quality of life (QoL) of elderly patients undergoing aortic valve replacement (AVR). METHODS: Records of patients ≥75 years old that underwent AVR from 2002 to 2006 were retrospectively analyzed. Functional status was classified with Barthel Index (BI). QoL was presumed as the self-perception of well-being after AVR. Independent predictors of mortality were identified using the Cox proportional hazards model. RESULTS: We included 114 patients, with a mean age of 78.5 ± 2.5 years. Seventy (59.8%) patients were females. Mean additive and logistic EuroSCORE were 7 ± 2 and 9 ± 7, respectively. Follow-up on vital status was achieved for 113 (99.1%) patients after a mean period of 47.2 ± 23.4 months. Twenty-seven (23.7%) patients died (including three operative deaths). Survival up to one, three, and five years of follow-up was 94.4%, 86.7%, and 76.1%, respectively. Multivariate analysis showed that pulmonary hypertension and diabetes were independent predictors of all-cause mortality. Information on BI score and QoL was obtained for 77 (89.5%) and patients. Among those, 69 (89.6%) were autonomous according to BI and 72 (93.5%) considered having had an improvement in QoL. CONCLUSION: Patients ≥75 years old undergoing AVR presented good medium-term survival. Predictors of an adverse outcome were significant pulmonary hypertension and diabetes. At follow-up, most achieved improvement of QoL and remained autonomous. These results stress that excellent long-term outcomes with AVR can be achieved in appropriately selected elderly patients.

An atypical presentation of infective endocarditis.

Infective endocarditis is a well-known clinical entity. However, despite improved diagnostic techniques and advances in treatment options, left-sided native valve infective endocarditis remains a serious disease with high morbidity and mortality, especially in cases caused by Staphylococcus aureus. The clinical heterogeneity of infective endocarditis sometimes prevents rapid recognition, correct diagnosis and timely treatment, which are essential to reduce the morbidity and mortality associated with this disease. We report the case of a 62-year-old man, admitted for atrial fibrillation with complete atrioventricular block, which was found to be the result of methicillin-resistant S. aureus mitral valve endocarditis, complicated by local extension of the infection, heart failure, systemic embolism and multiple organ failure.

Cardiac thrombus and conduction disorder in takotsubo cardiomyopathy.

Takotsubo cardiomyopathy is a reversible form of left ventricular dysfunction with an apparently benign natural history after left ventricular recovery. Rarely there are complications such as arrhythmias and apical thrombus. We describe a case of takotsubo cardiomyopathy complicated with apical thrombus and persistent complete atrioventricular block after improvement of left ventricular wall motion.

Trends in online search for multiple sclerosis symptoms - Is pain a hot topic?

Assessing the relative importance among different multiple sclerosis (MS) symptoms could guide the efficient allocation of health care resources. We aimed to evaluate the trends in web search behavior worldwide regarding MS symptoms, by querying Google Trends using search terms related to MS symptoms. The popularity of those symptoms was evaluated worldwide from 16/April/2017 through 3/April/2022. A comparison of all search terms revealed that "multiple sclerosis" pain displayed by far the highest relative search volume. Prompt screening and evidence-based interventions are necessary to evaluate pain and optimize quality of life in MS patients.

Late onset neuromyelitis optica spectrum disorders (LONMOSD) from a nationwide Portuguese study: Anti-AQP4 positive, anti-MOG positive and seronegative subgroups.

INTRODUCTION: Several neuroimmunological disorders have distinct phenotypes according to the age of onset, as in multiple sclerosis or myasthenia gravis. It is also described that late onset NMOSD (LONMOSD) has a different phenotype. OBJECTIVE: To describe the clinical/demographic characteristics of the LONMOSD and distinguish them from those with early onset (EONMOSD). METHODS: From a nationwide Portuguese NMOSD study we analyzed the clinical/demographic characteristics of the LONMOSD. RESULTS: From the 180 Portuguese patients 45 had disease onset after 50 years old, 80% were female. 23 had anti-AQP4 antibodies (51.1%), 13 anti-MOG antibodies (28.9%) and 9 were double seronegative (20.0%). The most common presenting phenotypes in LONMOSD were transverse myelitis (53.3%) and optic neuritis (26.7%), without difference from EONMOSD (p = 0.074). The mean EDSS for LONMOSD was 6.0 (SD=2.8), after a mean follow-up time of 4.58 (SD=4.47) years, which was significantly greater than the mean EDSS of EONMOSD (3.25, SD=1.80)(p = 0.022). Anti-AQP4 antibodies positive LONMOSD patients had increased disability compared to anti-MOG antibodies positive LONMOSD (p = 0.022). The survival analysis showed a reduced time to use a cane for LONMOSD, irrespective of serostatus (p<0.001). CONCLUSIONS: LONMOSD has increased disability and faster progression, despite no differences in the presenting clinical phenotype were seen in our cohort.

Inhibition of notch signaling in glioblastoma targets cancer stem cells via an endothelial cell intermediate.

Glioblastoma multiforme (GBM) is a highly heterogeneous malignant tumor. Recent data suggests the presence of a hierarchical organization within the GBM cell population that involves cancer cells with stem-like behavior, capable of repopulating the tumor and contributing to its resistance to therapy. Tumor stem cells are thought to reside within a vascular niche that provides structural and functional support. However, most GBM studies involve isolated tumor cells grown under various culture conditions. Here, we use a novel three-dimensional organotypic "explant" system of surgical GBM specimens that preserves cytoarchitecture and tumor stroma along with tumor cells. Notch inhibition in explants results in decreased proliferation and self-renewal of tumor cells but is also associated with a decrease in endothelial cells. When endothelial cells are selectively eliminated from the explants via a toxin conjugate, we also observed a decrease in self-renewal of tumor stem cells. These findings support a critical role for tumor endothelial cells in GBM stem cell maintenance, mediated at least in part by Notch signaling. The explant system further highlighted differences in the response to radiation between explants and isolated tumor neurospheres. Combination treatment with Notch blockade and radiation resulted in a substantial decrease in proliferation and in self-renewal in tumor explants while radiation alone was less effective. This data suggests that the Notch pathway plays a critical role in linking angiogenesis and cancer stem cell self-renewal and is thus a potential therapeutic target. Three-dimensional explant systems provide a novel approach for the study of tumor and microenvironment interactions.

Willingness to be vaccinated against COVID-19: An exploratory online survey in a Portuguese cohort of multiple sclerosis patients.

BACKGROUND: Little is known about MS patients' acceptability of a COVID-19 vaccine. OBJECTIVE AND METHODS: An online survey was conducted among MS patients to study COVID-19 vaccine acceptability and its associated factors. RESULTS AND CONCLUSION: Among 256 participants, 80.9% of the patients were either definitely or probably willing to receive a COVID-19 vaccine. Most hesitant patients would consider being vaccinated under physician recommendation. Older patients and those with comorbidities seem to be more willing to get vaccinated. Moreover, vaccine acceptability was associated with participants' convictions and concerns about COVID-19, as well as previous vaccination practices.

TyPed study: Natalizumab for the treatment of pediatric-onset multiple sclerosis in Portugal.

BACKGROUND: A significant proportion of pediatric-onset multiple sclerosis (POMS) patients do not respond to first-line disease-modifying therapies. Clinical trials showed that natalizumab is effective and safe in adults, but there are limited clinical trial data for children. Natalizumab is currently prescribed off-label for POMS. We aimed to characterize the effectiveness, safety and tolerability of natalizumab in all POMS cases treated in Portugal (from 2007 to 2018). METHODS: Data from clinical records were retrospectively collected for all POMS cases treated with natalizumab in Portugal. RESULTS: Twenty-one patients were included, 14 (67%) of which were female. The median age at POMS diagnosis was 13 years old. The median duration of treatment with natalizumab was 2 years and 3 months. Median Expanded Disability Status Scale score decreased from 1.5 to 1.0 after 24 months. The Annualized Relapse Rate decreased from 1.31 events/patient/year before treatment with natalizumab to 0 after 12 months of treatment and to 0.04 after 24 months. No gadolinium-enhancing lesions or new or enlarged T2 hyperintense lesions were observed in 8/8 patients (100%) after 12 months, and 4/5 (80%) after 24 months. There was one possible serious adverse event, which did not require dose adjustment. Five patients discontinued treatment due to positive anti-JCV (JC virus) antibody JC serostatus. CONCLUSION: Natalizumab may be an effective and safe disease-modifying therapy for POMS. Our results are in line with data published for the adult population, as well as with similar observational studies in pediatric populations in other regions.

RISCOP-Cognitive profile in a Portuguese cohort of radiological isolated syndrome patients: A case-control study.

INTRODUCTION: Radiologically isolated syndrome (RIS) refers to the incidental discovery of white matter lesions suggestive of MS, on brain MRI, in asymptomatic patients. Recent studies suggest similar features of cognitive impairment between RIS and MS patients. Also, lower levels of health-related quality of life (QOL) and fatigue are reported in such patients. AIMS: characterize and compare the cognitive profile of a multicentric Portuguese cohort of RIS patients with a control group. METHODS: multicentric comparative study of a cohort of adult patients with RIS, and age and gender-matched controls followed in the headache outpatient clinic with prior MRI not fulfilling criteria for RIS diagnosis. We conducted interviews with participants, collected clinical data and applied the BICAMS battery and self-reported questionnaires (HADS, MFIS, MSQOL-54). RESULTS: we evaluated 31 patients with RIS (median age 46 years, IQR [(Dusankova et al., 2012-52], 72% women) and 19 control individuals (median age 32 years, IQR [(O'Jile et al., 2005-48], 71% women). Prevalence of cognitive impairment did not differ between groups (16% of the RIS and 10% of the controls, p=0.579). We found no differences between groups on the BICAMS tests, although the results of the California Verbal Learning Test (CVLT-II) score presented a trend to significance, with a lower value on the RIS group (53.9 vs. 59.3, p=0.066). There were no significant differences regarding fatigue, QOL, anxiety/depression scores. CONCLUSION: this is the first study on a Portuguese cohort of RIS patients assessing cognitive profile with BICAMS. A non-neglectable part of our cohort presented cognitive impairment. Our findings add to previous studies in suggesting that a more pronounced impairment of verbal memory and learning, evaluated by CVLT-II, may be present in RIS patients compared to controls. BICAMS should be assessed on future studies with larger cohorts.

Neuromyelitis optica spectrum disorders: A nationwide Portuguese clinical epidemiological study.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a rare disorder in which astrocyte damage and/or demyelination often cause severe neurological deficits. OBJECTIVE: To identify Portuguese patients with NMOSD and assess their epidemiological/clinical characteristics. METHODS: This was a nationwide multicenter study. Twenty-four Portuguese adult and 3 neuropediatric centers following NMOSD patients were included. RESULTS: A total of 180 patients met the 2015 Wingerchuk NMOSD criteria, 77 were AQP4-antibody positive (Abs+), 67 MOG-Abs+, and 36 seronegative. Point prevalence on December 31, 2018 was 1.71/100,000 for NMOSD, 0.71/100,000 for AQP4-Abs+, 0.65/100,000 for MOG-Abs+, and 0.35/100,000 for seronegative NMOSD. A total of 44 new NMOSD cases were identified during the two-year study period (11 AQP4-Abs+, 27 MOG-Abs+, and 6 seronegative). The annual incidence rate in that period was 0.21/100,000 person-years for NMOSD, 0.05/100,000 for AQP4-Abs+, 0.13/100,000 for MOG-Abs+, and 0.03/100,000 for seronegative NMOSD. AQP4-Abs+ predominated in females and was associated with autoimmune disorders. Frequently presented with myelitis. Area postrema syndrome was exclusive of this subtype, and associated with higher morbidity/mortality than other forms of NMOSD. MOG-Ab+ more often presented with optic neuritis, required less immunosuppression, and had better outcome. CONCLUSION: Epidemiological/clinical NMOSD profiles in the Portuguese population are similar to other European countries.

Prognostic value of kappa free light chains determination in first-ever multiple sclerosis relapse.

Given its highly variable clinical course, an unmet need for objective prognostic assessment in Multiple Sclerosis (MS) persists. In this work, we suggest that CSF kappa free light chains (KFLC) determination at first relapse may provide insight into future disease activity and disability worsening. We quantified KFLC by nephelometry in paired CSF/serum samples of 28 patients, collected within one month of first-ever MS relapse, and explored correlations with clinical data on disease activity, retrospectively registered across a median follow-up time of 79 months. We documented KFLC ratio (CSF-FKLC/Serum-KFLC) as an independent predictor of second relapse occurrence and disability worsening at follow-up, in this cohort.