Picturing the Multiple Sclerosis Patient Journey: A Symptomatic Overview.

Background: Multiple sclerosis (MS) presents a wide range of clinical symptoms, historically understood through long-term studies of earlier patient cohorts. However, due to improved diagnostic criteria, modern patients are diagnosed earlier and benefit from effective treatments, altering the disease's natural history. This study aimed to assess the clinical symptoms of MS patients in a modern population at various stages: before diagnosis, at diagnosis, during the disease course, and at the time of the survey. Methods: This was an observational study with retrospective and cross-sectional components; patients that fulfilled the 2017 revised McDonald criteria for MS completed a survey evaluating demographic and clinical data. Results: We included 163 patients, 69.9% female, with a mean age of 48.21 years; 87.1% had relapsing-remitting MS (RRMS), with a median EDSS of 2.0. Before diagnosis, 74.2% of patients experienced symptoms, mainly sensory issues (39.3%), fatigue (29.4%), and imbalance (27%). Motor and coordination symptoms were more common in progressive forms. At diagnosis, sensory (46.6%) and motor complaints (36.8%) were most prevalent. In RRMS and secondary progressive MS (SPMS), sensory and motor complaints predominated alongside imbalance, while primary progressive MS (PPMS) was characterized by motor, imbalance, and genitourinary symptoms. Throughout the disease, sensory symptoms were most common (76.1%), with fatigue (73%) and motor issues (62.6%) more prevalent in progressive forms. At the time of the survey, 50.7% of RRMS patients were asymptomatic, while progressive patients continued to experience motor symptoms, imbalance, and fatigue. Conclusions: The study reflects the modern spectrum of MS symptoms, consistent with previous research.

Exploring first-degree family history in a cohort of Portuguese Alzheimer's disease patients: population evidence for X-chromosome linked and recessive inheritance of risk factors.

BACKGROUND: Alzheimer's disease (AD) heritability is estimated to be around 70-80%. Yet, much of it remains to be explained. Studying transmission patterns may help in understanding other factors contributing to the development of AD. OBJECTIVE: In this study, we aimed to search for evidence of autosomal recessive or X- and Y-linked inheritance of risk factors in a large cohort of Portuguese AD patients. METHODS: We collected family history from patients with AD and cognitively healthy controls over 75 years of age. We compared the proportions of maternal and paternal history in male and female patients and controls (to search for evidence of X-linked and Y-linked inherited risk factors). We compared the risk of developing AD depending on parents' birthplace (same vs. different), as a proxy of remote consanguinity. We performed linear regressions to study the association of these variables with different endophenotypes. RESULTS: We included 3090 participants, 2183 cognitively healthy controls and 907 patients with AD. Men whose mother had dementia have increased odds of developing AD comparing to women whose mother had dementia. In female patients with a CSF biomarker-supported diagnosis of AD, paternal history of dementia is associated with increased CSF phosphorylated Tau levels. People whose parents are from the same town have higher risk of dementia. In multivariate analysis, this proxy is associated with a lower age of onset and higher CSF phosphorylated tau. CONCLUSIONS: Our study gives evidence supporting an increased risk of developing AD associated with an X-linked inheritance pattern and remote consanguinity.

SQSTM1 Pro392Leu presenting as a corticobasal syndrome with progressive nonfluent aphasia.

Corticobasal syndrome is generally considered to be a sporadic condition. There are familial and isolated genetic cases, associated with GRN, MAPT, c9orf72 or PNRP variants. Some reports implicate other genes: LRRK2, CHMP2B, GBA, CYP27A1, PSEN1, APP, TARDBP and TBK1. Here, we report a case of a patient carrying a SQSTM1 Pro392Leu variant. We report a 57-year-old right-handed-woman with a history of progressive speech impairment, marked right side rigidity and bradykinesia, with rest tremor and stimulus sensitive myoclonus. She had predominantly right-sided apraxia. She had right side agraphestesia and astereognosis. MRI showed asymmetrical left frontotemporoparietal atrophy. DaTSCAN showed predominantly left involvement, PiB-PET was negative. CSF NfL was of 9356.5pg/mL. She carried a heterozygous variant P392L in SQSTM1. This case report expands the spectrum of phenotypes associated with SQSTM1 pathogenic variants. It also expands the list of genes associated with corticobasal syndrome, supporting the involvement of the ubiquitin-proteasome system in this condition.

Natalizumab extended interval dosing: what about wearing-off effect?

BACKGROUND: Up to two thirds of patients with multiple sclerosis (MS) under natalizumab report a resurgence of symptoms at the end of the natalizumab cycle (wearing-off (WO) effect). At the outbreak of COVID-19, in line with the international recommendations for MS management, our centre switched all clinically stable patients on natalizumab therapy for more than one year from standard interval dosing (SID) to extended interval dosing (EID) with every six weeks infusions. This study aimed to evaluate the impact of EID in WO in MS patients under natalizumab. METHODS: An observational retrospective study in patients with MS under natalizumab on EID was conducted. A questionnaire regarding current (on EID) and past (on SID) experience of WO effect was applied. RESULTS: Seventy-six patients were included. No significant differences were found in the annual relapse rate after the switch to EID (p = 0.083). However, there was a significant increase in the proportion of patients complaining of WO from 38.2% to 56.6% (p = 0.001). Moreover, patients with WO on SID, referred a significant increase in severity (p = 0.019) and duration of WO symptoms (p = 0.029), due to an anticipation of the symptoms relative to the day of natalizumab infusion (p = 0.019), when switching to EID. Symptoms improved with treatment maintenance in 23.3% of patients; instead, a reduction in interval dosing was needed in 54.8% with symptom improvement. CONCLUSION: WO affects a significant proportion of MS patients under natalizumab. Its prevalence, severity, and duration increase on EID, therefore despite clinical effectiveness maintenance of this posology should be individualized.

Prevalence, Incidence, and Mortality of Multiple Sclerosis in Coimbra, Portugal.

Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system in young adults, representing the leading cause of nontraumatic disability in this population. The rising prevalence of MS worldwide makes it critical to recognize the absolute number of patients with MS, demanding the execution of a sustainable healthcare policy. In Portugal, only six studies evaluating MS rates were published, disclosing a prevalence of 64 cases per 100,000 persons and an incidence of 3.1 cases per 100,000 persons/year, but the mortality rates have not been reported. Thus, this observational, cross-sectional study aimed to assess MS prevalence, incidence, and mortality in the city of Coimbra, a region in the center of Portugal. Patients who fulfilled McDonald's Diagnosis Criteria (2017) for MS were recruited. Inclusion criteria were defined according to prevalence, incidence, and mortality studies. The baseline demographic and clinical characterization of the prevalence study population was performed. The MS prevalence rate in Coimbra was 143.45 cases per 100,000 inhabitants. Between 2018 and 2021, the cumulative incidence was 8.52 new cases per 100,000 persons/year. The mortality rate between 2018 and 2021 was 2.84 deaths per 100,000 inhabitants. MS prevalence and incidence in Coimbra are higher than reported in previous similar studies and comparable to Europe's mean prevalence and incidence.

Health Professionals' Motivational Strategies to Enhance Adherence in the Rehabilitation of People with Lower Limb Fractures: Scoping Review.

Patients with lower limb fractures require rehabilitation but often struggle with adherence to interventions. Adding motivational strategies to rehabilitation programs can increase patient adherence and enhance outcomes. This review aims to identify the motivational strategies used by health professionals in the rehabilitation of people with lower limb fractures. We used Arksey and O'Malley's methodological framework to structure and conduct this scoping review. The literature search was performed using the Scopus, CINAHL, MEDLINE, Nursing & Allied Health, and Cochrane Central Register of Controlled Trials databases. The final search was conducted in February 2023. A total of 1339 articles were identified. After selecting and analyzing the articles, twelve studies were included in this review. Health professionals use several strategies to motivate patients with lower limb fractures to adhere to rehabilitation programs. These strategies include building a therapeutic alliance, increasing patients' health literacy, setting achievable goals, personalizing the rehabilitation program, managing unpleasant sensations of exercise, using persuasion, providing positive reinforcement, avoiding negative emotional stimulation, and helping to seek support. The motivational strategies identified may help professionals to increase patient adherence to rehabilitation for lower limb fractures. This knowledge will allow these professionals to help patients overcome barriers to rehabilitation, enhance their motivation, and ultimately improve their recovery outcomes.

Montreal Cognitive Assessment in Mild Cognitive Impairment: Relationship with Cerebrospinal Fluid Biomarkers and Conversion to Dementia.

BACKGROUND: Mild cognitive impairment (MCI) is considered a prodromal state of dementia. Abnormal values of cerebrospinal fluid Alzheimer's disease biomarkers (CSF-AD-b) have been associated with a higher risk of conversion to dementia (due to Alzheimer's disease), but studies evaluating the ability of Montreal Cognitive Assessment (MoCA) in this task are lacking. OBJECTIVE: This study aims to investigate the relationship between MoCA and CSF-AD-b, as well as the ability of those tools to predict conversion to dementia. METHODS: Taking advantage of our MCI cohort with biological characterization on longitudinal follow-up (180 patients followed for 62.6 months during which 41.3% converted), we computed MoCA and MMSE z-scores, using Portuguese normative data. The performance in MoCA z-score was correlated with CSF-AD-b and the relative time to conversion and risk according to baseline characteristics were analyzed using Kaplan-Meier analysis and Cox regression models. RESULTS: MoCA z-scores were correlated with Aß42 (p = 0.026), t-tau (p = 0.033), and p-tau (p = 0.01). Impaired MMSE (p < 0.001) and MoCA z-scores (p = 0.019), decreased Aß42 (p < 0.001) and increased t-tau (p < 0.001) and p-tau (p < 0.001) were associated with shorter estimated time of conversion. Aß42 (p < 0.001) and MMSE z-scores (p = 0.029) were independent predictors of conversion. For those with at least 9 years of education, MoCA z-score (p = 0.004) (but not MMSE) was an independent predictor of conversion as well as Aß42. CONCLUSIONS: This study confirms the role of CSF-AD-b, namely Aß42, in predicting conversion from MCI to dementia and suggests the utility of MoCA in predicting conversion in highly educated subjects, supporting its use in the evaluation of MCI patients.

Nursing students' knowledge and attitudes toward older adults.

Nursing students, as the future healthcare workforce, hold immense potential in providing quality care to older adults and becoming advocates for promoting aging and public health, thus contributing significantly to addressing the multifaceted challenges of our aging society. Nurses' knowledge and attitudes about aging affect health care quality. Negative and unattractive representations of the social problems associated with aging contaminate nursing students' attitudes. Nursing schools are challenged to develop new curricula to prepare future nurses for the inherent complexity of an aging society. This study aims to assess the knowledge and attitudes of nursing students toward older adults and identify the variables that can influence these attitudes. Quantitative research was carried out through the application of an online survey using a cross-sectional descriptive research design. A total of 182 nursing students completed the online survey. Progression in the nursing course was statistically significant; the more students advanced, the more positive attitudes and knowledge they revealed about aging; 39% of students have daily contact with their grandparents; however, only 14.8% would like to work with older adults. Multiple linear regression revealed that the most important factor for positive attitudes and knowledge about aging was regular contact with grandparents, followed by progression in the nursing course. The students' age was not a significant factor in improving attitudes or expanding knowledge regarding older adults. In a multidimensional logic, the deepening of knowledge about aging and the socialization of students with older adults are central factors that should reinforce curricula in nursing education.

Enablers, barriers and strategies to build resilience among cancer survivors: a qualitative study protocol.

Cancer is a life-threatening illness affecting all dimensions of a person's health. Cancer survivors must build resilience to face this adversity and continue their life projects. The present study explores the enablers, barriers, and strategies to build resilience among cancer survivors. This qualitative, descriptive exploratory study will use purposive sampling to recruit cancer survivors and healthcare professionals from two hospital centers in Lisbon and Tagus Valley. Interviews will be conducted until data saturation occurs. Data analysis will be performed using an inductive content analysis process with the help of the QDA Miner Lite database. The findings from this study will generate knowledge that may help stakeholders to identify effective strategies to build resilience among cancer survivors. By implementing strategies to foster resilience, healthcare professionals can potentially promote positive adaptations to cancer by strengthening resilience enablers and reducing the impact of barriers.

Clinical Reasoning: A 24-Year-Old Pregnant Woman With Headache and Behavioral Change Progressing to Coma.

The broad differential diagnosis associated with progressive subacute encephalopathy can be intimidating, especially in a young, pregnant woman. In this case, a 24-year-old woman at 21 weeks of gestation presented with persistent, drug-resistant fronto-parietal headache, with subsequent progressive development of psychomotor lentification and inappropriate behavior. Physical examination was normal, as were routine laboratory parameters and CT findings, and these symptoms were initially interpreted in the context of chronic depression. Later, the patient developed generalized dystonia and fever, with rapid clinical deterioration, depression of consciousness and, eventually, progression to coma. This case emphasizes the complexity and challenges involved in the diagnostic approach to a patient with progressive subacute encephalopathy framed by worsening CNS symptoms. It highlights the clinical considerations and complementary investigation of various etiologies, in a step-by-step approach, ultimately leading to the final diagnosis. Early recognition and appropriate treatment of these conditions can lead to more favorable outcomes, particularly in gestating patients, where prompt intervention is crucial, and where critical decisions may have to be made regarding pregnancy and the safety of treatment options.

Reconsidering the role of blood-brain barrier in Alzheimer's disease: From delivery to target.

The existence of a selective blood-brain barrier (BBB) and neurovascular coupling are two unique central nervous system vasculature features that result in an intimate relationship between neurons, glia, and blood vessels. This leads to a significant pathophysiological overlap between neurodegenerative and cerebrovascular diseases. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease whose pathogenesis is still to be unveiled but has mostly been explored under the light of the amyloid-cascade hypothesis. Either as a trigger, bystander, or consequence of neurodegeneration, vascular dysfunction is an early component of the pathological conundrum of AD. The anatomical and functional substrate of this neurovascular degeneration is the BBB, a dynamic and semi-permeable interface between blood and the central nervous system that has consistently been shown to be defective. Several molecular and genetic changes have been demonstrated to mediate vascular dysfunction and BBB disruption in AD. The isoform ε4 of Apolipoprotein E is at the same time the strongest genetic risk factor for AD and a known promoter of BBB dysfunction. Low-density lipoprotein receptor-related protein 1 (LRP-1), P-glycoprotein, and receptor for advanced glycation end products (RAGE) are examples of BBB transporters implicated in its pathogenesis due to their role in the trafficking of amyloid-ß. This disease is currently devoid of strategies that change the natural course of this burdening illness. This unsuccess may partly be explained by our misunderstanding of the disease pathogenesis and our inability to develop drugs that are effectively delivered to the brain. BBB may represent a therapeutic opportunity as a target itself or as a therapeutic vehicle. In this review, we aim to explore the role of BBB in the pathogenesis of AD including the genetic background and detail how it can be targeted in future therapeutic research.

Blood biomarkers in mild cognitive impairment patients: Relationship between analytes and progression to Alzheimer disease dementia.

BACKGROUND AND PURPOSE: Blood-based biomarkers are promising tools for the diagnosis of Alzheimer disease (AD) at prodromal stages (mild cognitive impairment [MCI]) and are hoped to be implemented as screening tools for patients with cognitive complaints. In this work, we evaluated the potential of peripheral neurological biomarkers to predict progression to AD dementia and the relation between blood and cerebrospinal fluid (CSF) AD markers in MCI patients referred from a general neurological department. METHODS: A group of 106 MCI patients followed at the Neurology Department of Coimbra University Hospital was included. Data regarding baseline neuropsychological evaluation, CSF levels of amyloid ß 42 (Aß42), Aß40, total tau (t-Tau), and phosphorylated tau 181 (p-Tau181) were available for all the patients. Aß42, Aß40, t-Tau, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels were determined in baseline stored serum and plasma samples by commercial SiMoA (Single Molecule Array) assays. Progression from MCI to AD dementia was assessed at follow-up (mean = 5.8 ± 3.4 years). RESULTS: At baseline, blood markers NfL, GFAP, and p-Tau181 were significantly increased in patients who progressed to AD at follow-up (p < 0.001). In contrast, plasma Aß42/40 ratio and t-Tau showed no significant differences between groups. NfL, GFAP, and p-Tau181 demonstrated good diagnostic accuracy to identify progression to AD dementia (area under the curve [AUC] = 0.81, 0.80, and 0.76, respectively), which improved when combined (AUC = 0.89). GFAP and p-Tau181 were correlated with CSF Aß42. Association of p-Tau181 with NfL was mediated by GFAP, with a significant indirect association of 88% of the total effect. CONCLUSIONS: Our findings highlight the potential of combining blood-based GFAP, NfL, and p-Tau181 to be applied as a prognostic tool in MCI.

Nurses' Motivations, Barriers, and Facilitators to Engage in a Peer Review Process: A Qualitative Study Protocol.

Peer review supports the integrity and quality of scientific publishing. However, although it is a fundamental part of the publishing process, peer review can also be challenging for reviewers, editors, and other stakeholders. The present study aims to explore the nurses' motivations, barriers, and facilitators in engaging in a peer review process. This qualitative, descriptive exploratory study will be developed in partnerships with three research centers. Researchers followed the consolidated criteria for reporting qualitative research (COREQ) checklist to ensure the quality of this study protocol. According to the selection criteria, the purposive sampling will be used to recruit nurse researchers that act as peer reviewers for several scientific journals in various fields of knowledge. Interviews will be conducted until data have been sufficiently consistent with meeting the initial objectives. Researchers will develop a guide comprising a set of open-ended questions to collect participants' characteristics, descriptive review behavior, and perceptions regarding their motivations, barriers, and facilitators. Researchers will analyze data using an inductive process of content analysis with the help of the QDA Miner Lite database. Findings from this study will generate knowledge that may help stakeholders identify facilitating factors and barriers and guide the development of strategies to remove or minimize these barriers.

Addressing Ageism-Be Active in Aging: Study Protocol.

Ageism refers to stereotyping (how we think), prejudice (how we feel), and discrimination (how we act) against people based on their age. It is a serious public health issue that can negatively impact older people's health and quality of life. The present protocol has several goals: (1) adapt the Ambivalent Ageism Scale for the general Portuguese population and healthcare professionals; (2) assess the factorial invariance of the questionnaire between general population vs. healthcare professionals; (3) evaluate the level of ageism and its predictors in the general population and evaluate the level of ageism and its predictors in healthcare professionals; (4) compare the levels of ageism between groups and the invariance between groups regarding the explanatory model of predictors of ageism. This quantitative, cross-sectional, descriptive, observational study will be developed in partnership with several Healthcare Professional Boards/Associations, National Geriatrics and Gerontology Associations, and the Universities of the Third Age Network Association. The web-based survey will be conducted on a convenience sample recruited via various social media and institutional channels. The survey consists of three questionnaires: (1) Demographic data; (2) Ambivalent Ageism Scale; (3) Palmore-Neri and Cachioni questionnaire. The methodology of this study will include translation, pilot testing, semantic adjustment, exploratory and confirmatory factor analysis, and multigroup analysis of the Ambivalent Ageism Scale. Data will be treated using International Business Machines Corporation (IBM®) Statistical Package for the Social Sciences (SPSS) software and Analysis of Moment Structures (AMOS). Descriptive analysis will be conducted to assess the level of ageism in the study sample. The ageism levels between the two groups will be compared using the t-student test, and two Structural Equation Modeling will be developed to evaluate the predictors of ageism. Assessing ageism is necessary to allow healthcare professionals and policymakers to design and implement strategies to solve or reduce this issue. Findings from this study will generate knowledge relevant to healthcare and medical courses along with anti-ageism education for the Portuguese population.

Needs and expectations of family caregivers of cancer patients in palliative care: A study protocol.

Cancer has an associated burden that continues to grow, affecting patients, family caregivers, and the individual's community. The family caregivers' unmet needs may harmfully jeopardize their well-being and the patient's health outcomes. Therefore, it is essential to understand the needs and expectations of family caregivers of cancer patients to develop and improve care practices. The present study aims to explore the needs and expectations of family caregivers of cancer patients in palliative care. This qualitative, descriptive exploratory study will use purposive sampling to recruit family caregivers and healthcare professionals from the palliative care units of two hospital centers in Lisbon and Tagus Valley. First, the Focus group will be performed until data saturation occurs. Then, a conventional thematic analysis will be applied to analyze data with the help of the coding software QDA Miner Lite database. This study's findings will help identify gaps in care and provide data that can support healthcare professionals in providing evidence-based centered care to family caregivers. It can also generate knowledge that may help stakeholders to develop a comprehensive support system for cancer survivors in palliative care and their family caregivers.

Posterior reversible encephalopathy syndrome following Miller-Fisher syndrome.

A 71-year-old woman presented to the emergency room with dysphonia, diplopia, dysphagia and generalised weakness since that day. Neurological examination revealed eye adduction limitation, ptosis, hypoactive reflexes and gait ataxia. Blood and cerebrospinal fluid analysis and brain CT were normal. Electromyography revealed a sensory axonal polyneuropathy. She was diagnosed with Miller-Fisher syndrome (MFS) and started on intravenous immunoglobulin. Two days after intravenous immunoglobulin treatment was completed, she developed a sustained hypertensive profile and presented a generalised tonic-clonic seizure. Brain MRI was suggestive of posterior reversible encephalopathy syndrome (PRES) and supportive treatment was implemented with progressive improvement. PRES may be a possible complication of MFS not only due to autonomic and inflammatory dysfunctions, but also as a consequence of its treatment. Patients with MFS should be maintained under close surveillance, especially in the first days and preferably in intermediate care units.

Hospital admissions 2000-2014: A retrospective analysis of 288 096 events in patients with dementia.

INTRODUCTION: Dementia is a leading cause of disability worldwide. It is associated with an increased risk of hospitalization, imposing a significant burden on healthcare systems. The evidence on the long-term evolution of this issue and broadly on healthcare systems is currently limited. This study aims to describe the hospitalizations of people who received a diagnosis of dementia admitted to public general hospitals in a western European country with universal health coverage, over more than a decade. METHODS: This retrospective observational study analyzed all inpatient episodes from 2000 to 2014 with a primary or secondary diagnosis of dementia using a national hospitalization database from mainland Portuguese public hospitals. RESULTS: A total of 288 096 hospital admissions were registered. Hospitalization rates increased 4.7 times throughout the study period. Pneumonia and urinary tract infections were the most frequent main diagnoses, while dementia itself was the cause of admission in a minority (6.8%) of cases. Cerebrovascular disease, diabetes without chronic complications, and congestive heart failure were the most prevalent comorbidities; 5.9% of patients with dementia admitted to hospital underwent a surgical procedure, orthopedic surgeries being the most frequent. The median length of hospital stay was 8.0 days, and in-hospital mortality rate was 16.1%. CONCLUSIONS: Dementia patients represent a significant amount of hospital admissions. Most leading causes of hospital admissions are preventable if timely diagnosed and could be effectively managed in the outpatient setting. These findings may be useful for healthcare resource planning and allocation. Further research should drive evidence-based reorganization of health care systems.