Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum.

Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common and clinically distinct form of familial spastic paraplegia that is linked to the SPG11 locus on chromosome 15 in most affected families. We analyzed 12 ARHSP-TCC families, refined the SPG11 candidate interval and identified ten mutations in a previously unidentified gene expressed ubiquitously in the nervous system but most prominently in the cerebellum, cerebral cortex, hippocampus and pineal gland. The mutations were either nonsense or insertions and deletions leading to a frameshift, suggesting a loss-of-function mechanism. The identification of the function of the gene will provide insight into the mechanisms leading to the degeneration of the corticospinal tract and other brain structures in this frequent form of ARHSP

Persistent trigeminal artery in a patient with posterior circulation stroke treated with rt-PA: case report

Background A persistent trigeminal artery (PTA) is a non-involuted embryonic vessel that connects the cavernous part of the internal carotid artery with the posterior circulation. In the adult it is associated with multiple pathological conditions including trigeminal neuralgia, ophthalmoplegia, hypopituitarism, intracavernous fistula, brain aneurysms and posterior circulation strokes. The latter may occur through steal phenomena or thrombosis in the anterior circulation. PTA associated vertebrobasilar hypoplasia has yet to be associated to TIA like events, however, in the reported case, that seems to be the case with reported vertigo being probably linked to vertebrobasilar insufficiency. Case report We present a case of an 82-year-old man with sudden onset neurological deficits, including left hemiparesis with crural predominance, vertical nystagmus, right internuclear ophthalmoplegia, dysarthria and dysmetria on the left arm. CT angiography disclosed basilar artery hypoplasia in the proximal two thirds and a persistent trigeminal artery. He was diagnosed with acute ischemic stroke. He was submitted to rt-PA with partial reversion of deficits. Conclusion The ischemic events related to PTA remain a rare cause of stroke with specific pathophysiological mechanisms and implications. They may occur through steal phenomena or thrombosis in the anterior circulation. Upon literature review, in the described case both mechanisms seem possible, however the transient episodes of vertigo could have been the first sign of vertebrobasilar insufficiency.No funding was obtained for this article

Sociodemographic and psychological characteristics influencing patients' willingness to participate in clinical trials

Background/Aims Clinical trials are fundamental for the development of new medicines and patient participation is based on free consent. Our study sought to identify psychological characteristics that may influence patient willingness to participate in a clinical trial. Methods A total of 100 participants were invited to participate with 80% positive response rate. The psychological characteristics of each patient were evaluated using the following validated psychometric scales: Self-Efficacy Scale, Curiosity, Exploration Inventory-Trait, Social Support Satisfaction, State-Trait Anxiety Inventory and Social Avoidance and Distress, and Fear of Negative Evaluation. Results Patients who agreed to participate in the clinical trial were significantly younger than those who refused (p=0.028). There were no differences in sex, lifestyle, employment status, monthly income or education. After adjusting for age and sex, patients who agreed to participate scored significantly higher in the following: self-efficacy total score (p<0.001), effectiveness in adversity (p<0.001), social effectiveness (p<0.001) and initiation and persistence (p<0.001); social support total score (p<0.001), family satisfaction (p=0.015), friendship satisfaction (p<0.001), social activities satisfaction (p=0.002) and intimacy (p<0.001); total curiosity score (p<0.001), absorption (p<0.001) and exploration (p<0.001). Compared with patients who agreed to participate, those who refused scored significantly higher for both state (p<0.001) and trait anxiety (p<0.001), fear of negative evaluation (p<0.001) and social avoidance and distress (p<0.001). Conclusions Patients who were willing to participate in clinical trials exhibited different psychological characteristics to patients who refused. Specifically, they were more curious and self-efficacious, less anxious and reported a higher level of social support than patients who declined to participate. Identifying characteristics that condition the individual's decision to participate in a clinical trial has important implications for the development of patient-focused communication strategies and improved recruitment approaches. ©This work was supported by BlueClinical, Ltd

Systematic review and meta-analysis on the association between chronic low back pain and cognitive function

This study aimed to identify and assess the evidence on the association between idiopathic chronic low back pain (LBP) and cognitive function in individuals with LBP. A secondary aim was to explore whether changes in cognitive function are associated with pain characteristics and psychological factors (eg, catastrophizing and fear of movement). Eleven studies were included in this systematic review, and four meta-analyses were conducted. Low to very low-quality evidence suggests impaired cognitive function in individuals with LBP compared to asymptomatic controls for problem solving (k = 5; d = 0.33; CI = 0.16–0.50; z = 3.85 p = 0.0001), speed of information processing (k = 5; d = 0.44; CI = 0.22–0.65; z = 4.02 p < 0.0001), working memory (k = 6; d = 0.50; CI = 0.34–0.66; z = 6.09 p < 0.0001), and delayed memory (k = 3; d = 0.34; CI = 0.07–0.6, z = 2.49 p = 0.02). The association between LBP intensity and psychological factors and cognitive function was inconclusive. More studies are needed to explore these associations and improve evidence in this field. The results of this study suggest that cognitive aspects should be considered during the rehabilitation process of patients with LBP and raise further questions, including whether individuals with LBP are at a greater risk of developing dementia or whether targeting cognitive function will increase the probability of success of LBP treatment. These questions should, also, be considered in future studies.This work was supported by the National Funds through FCT – Fundação para a Ciência e a Tecnologia, I.P., within CINTESIS, R&D Unit (reference DFA/BD/8869/2020)

The impact of users’ cognitive function on evaluator perceptions of usability

To explore the association between the user’s cognitive function and usability reported by the evaluator. A cross-sectional study was conducted with a community-based sample. Data about participants’ age, sex, education, sleep quantity, subjective memory complaints, and cognitive function were collected. A usability session was conducted to evaluate a digital solution called Brain on Track. Independent linear-regression analyses were used to explore univariable and multivariable associations between evaluator-reported usability assessment and the users’ cognitive function, age, sex, education, sleep quantity, and subjective memory complaints. A total of 238 participants entered this study, of which 161 (67.6%) were females and the mean age was 42 (SD 12.9) years old. All variables (age, education, sleep quantity, subjective memory complaints and cognitive function) except sex were significantly associated with evaluator-reported usability in the univariable analysis (p < 0.05). Cognitive function, age, education, and subjective memory complaints remained significant in the multivariable model (F = 38.87, p < 0.001) with an adjusted R2 of 0.391. Cognition scores alone showed an adjusted R2 of 0.288. This work suggests that cognitive function impacts evaluator reported usability, alongside other users’ characteristics and needs to be considered in the usability evaluation. © 2022, The Author(s).This study was partially supported by the Águeda City Council as part of a community cognitive screening program

Validity and reliability of a digital solution for cognitive assessment: The Brain on Track®

"Background: Cognitive assessment and the early detection of cognitive impairments have been enhanced by the use of remote digital solutions. The Brain on Track® is one of these digital solutions used in clinical practice for online screening and monitoring of cognitive functioning. Objectives: This study aimed to explore the validity and reliability of the Brain on Track® computerized test on a tablet device in adults. Methods: A community sample of 54 young adults, 51 middle-aged adults, and 50 older adults were invited to attend in two assessment sessions. The first session included data collection on sociodemographic data, user digital literacy, Brain on Track® on the computer and on the tablet device, and usability from the user and moderator perspective. The second session included the Montreal Cognitive Assessment Questionnaire (MoCA) and a second completion of the Brain on Track® on tablet to assess the criterion validity and test-retest reliability. Hypothesis testing was used to assess construct validity. Results: A weak to moderate correlation was found between the Brain on Track® tablet score and the MoCA. The ICC was 0.72, 0.84, and 0.79, and Cronbach's alpha was 0.84, 0.83, and 0.89 in young adults, middle-aged adults, and older adults, respectively. Conclusions: This study suggested that the Brain on Track® administered using a tablet device has criterion validity, particularly in middle-aged and older adults, and internal consistency and test-retest reliability in adults of any age group."The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Portuguese Recovery and Resilience Plan (PRR) and by the NextGenerationEU European Funds, through the “Agendas para a Inovação Empresarial” incentive system, under project HfPT—Health from Portugal (02/C05-i01.01/2022.PC644937233-00000047)

Study protocol for a pilot randomised controlled trial evaluating the feasibility and effectiveness of non-pharmacological interventions to recover functionality after a transient ischaemic attack or a minor stroke: the 'Back to Normal' trial

Introduction Transient ischaemic attack (TIA) and minor stroke are frequently assumed as temporary or non-disabling events. However, evidence suggests that these patients can experience relevant impairment and functional disability. Therefore, the present study aims to evaluate the feasibility and effectiveness of a 3-month multidomain intervention programme, composed of five non-pharmacological strategies, aimed at accelerating return to pre-event level of functionality in patients with TIA or minor stroke. Methods and analysis Patients diagnosed with a TIA or a minor stroke are being recruited at the emergency or neurology departments of the Hospital Pedro Hispano, located in Matosinhos, Portugal (n=70). Those who accept to participate will be randomly allocated to two groups (1:1): (a) Intervention-receives a 3 months combined approach, initiating early post-event, composed of cognitive training, physical exercise, nutrition, psychoeducation and assessment/correction of hearing loss; (b) Control-participants will not be subject to any intervention. Both groups will receive the usual standard of care provided to these diseases. Recruitment began in May 2022 and is expected to continue until March 2023. Socio-demographic characteristics, lifestyles, health status, cognitive function, symptoms of anxiety and depression and quality of life will be assessed; as well as anthropometry, blood pressure and physical condition. Time to complete or partial recovery of instrumental activities of daily living will be assessed using an adapted version of the Frenchay Activities Index. All participants will be evaluated before the intervention and after 3 months. Ethics and dissemination This study was approved by the Ethics Committee of the Local Health Unit of Matosinhos (Ref. 75/CES/JAS). Written informed consent will be required from all the participants; data protection and confidentiality will be also ensured. The findings of this project are expected to be submitted for publication in scientific articles, and the main results will be presented at relevant scientific meetings. Trial registration number NCT05369637.This work was financed by national funds through the FCT - Foundation for Science and Technology, I.P., within the scope of projects UIDB/04750/2020 and LA/P/0064/2020. It was also supported by the Portuguese Stroke Society under the research scholarship Prof. Castro Lopes in cerebrovascular disease. The MIND-Matosinhos project was supported by 'Portugal Inovacao Social' and co-funded by the Operational Program Social Inclusion and Employment, Portugal 2020 and European Union, through the European Social Fund (POISE-03-4639-FSE-000793). Funders will not have any influence on the study design, execution, interpretation of data, writing and publication of manuscripts

Recruitment and retention in a multidomain intervention for post-TIA and minor stroke: turning challenges into lessons

This study was funded by FCT - Fundação para a Ciência e a Tecnologia, I.P. (UIDB/04750/2020 and LA/P/0064/2020; DOI: https://doi.org/10.54499/UIDB/04750/2020 and https://doi.org/10.54499/LA/P/0064/2020) and by the Portuguese Stroke Society, under the scholarship “Prof. Castro Lopes's research scholarship in cerebrovascular disease”. The “MIND-Matosinhos” project was supported by Portugal Inovação Social and co-funded by the Operational Programme Social Inclusion and Employment, Portugal 2020 and European Union, through the European Social Fund, as well as by the Matosinhos City Council (POISE-03-4639-FSE-000793). ARC was supported by FCT under the Stimulus of Scientific Employment – Individual Support Programme (2022.03483.CEECIND/CP1732/CT0002; DOI: https://doi.org/10.54499/2022.03483.CEECIND/CP1732/CT0002)

Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion

Neurotransmission and secretion of hormones involve a sequence of protein/lipid interactions with lipid turnover impacting on vesicle trafficking and ultimately fusion of secretory vesicles with the plasma membrane. We previously demonstrated that sphingosine, a sphingolipid metabolite, promotes formation of the SNARE complex required for membrane fusion and also increases the rate of exocytosis in isolated nerve terminals, neuromuscular junctions, neuroendocrine cells and in hippocampal neurons. Recently a fungi-derived sphingosine homologue, FTY720, has been approved for treatment of multiple sclerosis. In its non-phosphorylated form FTY720 accumulates in the central nervous system, reaching high levels which could affect neuronal function. Considering close structural similarity of sphingosine and FTY720 we investigated whether FTY720 has an effect on regulated exocytosis. Our data demonstrate that FTY720 can activate vesicular synaptobrevin for SNARE complex formation and enhance exocytosis in neuroendocrine cells and neurons

Prevalence and Causes of Cognitive Impairment and Dementia in a Population-Based Cohort From Northern Portugal

Background: Vascular disease may play an important role in the epidemiology of dementia in countries with high stroke incidence, such as Portugal. Objective: To assess the prevalence and etiology of cognitive impairment in a population-based cohort from Portugal. Methods: Individuals ≥55 years (n = 730) from the EPIPorto cohort were assessed using the Mini-Mental State Examination and the Montreal Cognitive Assessment. Those scoring below the age-/education-adjusted cutoff points were further evaluated to identify dementia or mild cognitive impairment (MCI) and to define its most common causes. Results: Thirty-six cases of MCI/dementia were identified, corresponding to adjusted prevalences of 4.1% for MCI and 1.3% for dementia. The most common cause of MCI/dementia was vascular (52.8%), followed by Alzheimer’s disease (36.1%). Conclusion: These findings highlight the importance of vascular cognitive impairment in the epidemiology of dementia in Portugal and carry an important public health message regarding its prevention and management, possibly extending to other countries with a high-stroke burden.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research project was financed by the Programa Operacional Competitividade e Internacionalização (POCI) (POCI-01-0145-FEDER-016867), the Programa Operacional Regional do Norte 2014/2020 (NORTE 2020) (NORTE-01-0145-FEDER-000003) and by the Fundação para a Ciência e a Tecnologia, in the context of the Epidemiology Research Unit—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; FCT UID/DTP/04750/2013), and the PhD Grant SFRH/BD/119390/2016 (Natália Araújo), co-funded by the FCT and the POCH/FSE Program