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Pannexin 1 (PANX1) is an ion and metabolite membrane channel and scaffold protein enriched in synaptic compartments of neurons in the central nervous system. In addition to a well-established link between PANX1 and synaptic plasticity, we recently identified a role for PANX1 in the regulation of dendritic spine stability. Notably, PANX1 and its interacting proteins are linked to neurological conditions involving dendritic spine loss. Understanding the dual role of PANX1 in synaptic function and morphology may help to shed light on these links. We explore potential mechanisms, including PANX1's interactions with postsynaptic receptors and cytoskeleton regulating proteins. Finally, we contextualize PANX1's dual role within neurological diseases involving dendritic spine and synapse dysfunction.

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AIM: To develop a Theory of Change (ToC) pathway to facilitate the development of a multi-component intervention package supporting pressure Ulcer (PU) risk identification and management, in partnership with people with Long Term Neurological Conditions (LTNC) who self-manage care and live at home, their informal carers and PAs. METHODS: A participatory approach, with extensive input from those whose lives are the focus of the research, was used throughout the 4 interlinked work packages (WP): Iterative data analysis was undertaken with emerging findings from each WP informing subsequent stages of the study. FINDINGS: Overall, 74 participants contributed across the 4 WPs, incorporating 31 Service Users (SU), 8 carers, 9 Personal Assistants (PAs) and 26 professional stakeholders. We identified 8 key themes related to PU prevention, incorporating, learning, safe routines, third sector and peer support, navigating complex systems, adapting and reacting to change, perceptions of risk, risk negotiation and supporting roles. The findings indicate systemic and professional barriers which hamper people's ability to self-care and seek help. CONCLUSIONS: The study highlights the complexities and impact of managing PU prevention activities at home for people with LTNC and areas of learning for health professionals and systems. By understanding these complexities we developed a systems map, identified resource requirements and illustrated a Theory of Change (ToC) pathway, to underpin future work to develop and user test an interactive, multi-component intervention.

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Complex walking tasks, including change of direction, patterns and rhythms, require more attentional resources than simple walking and significantly impact walking performance, especially among ageing and neurological populations. More studies are focusing on complex walking situations, with or without the addition of cognitive tasks, creating a multitude of walking situations. Facing the lack of a clear and extensive definition of complex walking, this narrative review aims to identify and more precisely characterize situations and related tests, gain a better understanding of the behavioral adaptations in ageing and neurological populations, and report the clinical applications of complex walking. Based on the studies gathered, we propose a framework that categorizes the different forms of complex walking, considering whether a cognitive task is added or not, as well as the number of distinct objectives within the situation. We observed that combining complex walking tasks with a cognitive assignment places even greater strain on attentional resources, resulting in a more pronounced decline in walking or cognitive performance, or both. This work highlights the relevance of the complex walking as a simple tool for the early detection of cognitive impairments and the risk of falls, and its potential value in cognitive-motor rehabilitation. Future studies should explore the diversity of complex walking tasks in real-life simulated through extended virtual environments.

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This pilot study assessed the feasibility and functional benefits of a twice-weekly, 12-week, virtual, seated, group-based Pilates program in persons with mild to severe multiple sclerosis (MS). Participants were randomized into either a Pilates-only group or a Pilates group, which also incorporated hip and shoulder-cuff activation exercises. Process, management, and scientific-feasibility metrics were analyzed descriptively. Functional outcomes, physical activity, and MS-related outcomes (impact, fatigue, and quality of life) were measured pre- and postintervention and analyzed using mixed-effects models, analysis of variance, and cluster analysis. Twenty-two participants completed baseline testing. Sixteen completed the intervention and postintervention testing. Collapsed across groups, analyses demonstrated improvements in the Timed 25-Foot Walk (36%), Timed Up-and-Go (13%), and the Berg Balance Scale (10%, statistically significant). Neither between-groups differences nor physical activity or MS outcome changes were significant. Participants reported high satisfaction. Findings suggest that virtual, seated Pilates is feasible and may confer balance benefits to individuals with MS.

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Multivariate pattern analysis (MVPA) of electroencephalographic (EEG) data represents a revolutionary approach to investigate how the brain encodes information. By considering complex interactions among spatio-temporal features at the individual level, MVPA overcomes the limitations of univariate techniques, which often fail to account for the significant inter- and intra-individual neural variability. This is particularly relevant when studying clinical populations, and therefore MVPA of EEG data has recently started to be employed as a tool to study cognition in brain disorders. Here, we review the insights offered by this methodology in the study of anomalous patterns of neural activity in conditions such as autism, ADHD, schizophrenia, dyslexia, neurological and neurodegenerative disorders, within different cognitive domains (perception, attention, memory, consciousness). Despite potential drawbacks that should be attentively addressed, these studies reveal a peculiar sensitivity of MVPA in unveiling dysfunctional and compensatory neurocognitive dynamics of information processing, which often remain blind to traditional univariate approaches. Such higher sensitivity in characterizing individual neurocognitive profiles can provide unique opportunities to optimise assessment and promote personalised interventions.

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BACKGROUND: Prion diseases are a group of rare, neurodegenerative conditions that are invariably fatal and cause a variety of symptoms, which can prove challenging to control. Through this paper, we aim to review the current evidence regarding pharmacological management of neuropsychiatric and motor symptoms of prion disease as well as draw on experts' and relatives' experience, to evaluate the current evidence and provide recommendations moving forwards. METHODS: A scoping review of the literature for pharmacological management of symptoms was conducted using the systematic review tool, COVIDENCE, with searches conducted through four databases. 120 papers were selected for inclusion, and data extraction was carried out by two independent reviewers. Given the lack of high-quality data and small numbers, no further attempt at statistical analysis was made, and results are presented in a thematic synthesis. RESULTS: Although a broad range of approaches and pharmacotherapies are trialled to manage these challenging symptoms, there are patterns emerging of some efficacy seen with the use of benzodiazepines, antipsychotic and anticonvulsant medications in both motor and neuropsychiatric symptoms in prion disease. These approaches and associated challenges were reflected in international expert opinion that was gathered via online survey. CONCLUSION: There continues to be a paucity of good-quality evidence and we suggest a need for longitudinal, population-based and standardised research to allow a robust evidence base, which in turn will guide excellent symptom control and end of life care for this group of complex patients.

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Background and Purpose: Currently there are approximately one billion people worldwide affected by a neurological condition. These conditions may result in a variety of impairments that require assessment and management from a physiotherapist. However, there is a lack of consensus in the literature as to what domains physiotherapists working in clinical settings include in their assessment of this population, with only five domains identified in a recent systematic review. This study aimed to explore current physiotherapy assessments in people with neurological conditions, including barriers, enablers, and influencing factors. Methods: A National online survey of Australian physiotherapists who assessed adults with neurological conditions in their clinical practice. Results: A total of 212 respondents from all states in Australia completed the survey. The mean (SD) age was 35.7 (9.6) years, and the majority were female (85.4%). Respondents worked across various settings assessing stroke most frequently (58.0%). Study results demonstrated variability in assessment practice, with a number of assessment domains being assessed more commonly including balance, muscle strength, gait, falls and safety, function, goal setting, range of movement, pain, co-ordination, activity tolerance, postural alignment and symmetry, and the upper limb. Experienced physiotherapists and those in rural and remote settings included fewer domains in their assessments. On the other hand, physiotherapists in the community setting included certain domains more frequently than those in other settings. Barriers and enablers were related to therapist caseload, knowledge, and intrinsic patient factors. Discussion: There is variability in domains assessed by Australian physiotherapists, with an emerging consensus for a number of assessment domains. Study results suggest that clinical experience, geographical location, and clinical setting may play a role in the assessment patterns observed. Implications on Physiotherapy Practice: There is little evidence to support what physiotherapists assess in practice, in different settings, in different states within Australia. This study indicates that experience, geographical location, and clinical setting affect the number and types of domains included in the assessment. Further research is needed to develop a consensus on best practices.

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Management of continuous focal seizure activity provides a unique challenge in palliative medicine. In cases where the patient is conscious and would prefer to remain so, we need to balance seizure-control with the sedating side effects of anti-seizure medications. Here we present a case in which subcutaneous lacosamide was given as part of a multi-modal treatment regime for a patient with continuous focal seizure activity. Lacosamide is a relatively new anti-seizure medication, that, unlike some anticonvulsants, has few drug interactions, is relatively non-sedating, and has physicochemical properties compatible with administration by the subcutaneous route. This case report adds to the very limited existing literature on the administration of lacosamide by the subcutaneous route. We conclude that lacosamide potentially provides an attractive option to contribute to the individualised care of this group of patients, and it may also have a role in the management of neuropathic pain where the enteral route is not available.

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BACKGROUND: Patients requiring enteral nutrition (EN) after neurological insults experience feeding interruptions, contributing to inadequate nutrition delivery. This prospective cohort study investigated if volume-based enteral feeding (VBF) improved the delivery of prescribed EN volume in ward patients with acute neurological conditions. METHODS: Over two sequential periods, the usual care group received standard continuous rate-based feeding, and the intervention group received VBF with bi-daily EN rate adjustments to achieve target daily volume. The primary outcome was percentage of prescribed daily EN formula volume delivered. Differences in energy and protein provision, weight, malnutrition and safety were explored. An evaluation survey captured nurse acceptability of the protocol. RESULTS: The intervention group (n = 32) achieved greater median interquartile range (IQR) EN adequacy of prescribed volume at 92% (88-97) compared to 67% (54-78) for usual care (n = 35) (p < 0.001). VBF compared to rate-based feeding resulted in patients receiving more kilojoules (131 [121-138] kJ/kg vs. 84 [64-99] kJ/kg; p < 0.001) and protein (1.3 [1.2-1.5] g/kg vs. 0.9 [0.6-1.1] g/kg; p < 0.001). There were no differences in gastrointestinal intolerance between groups. Compliance to the VBF protocol was 90%, and 78% of staff reported high confidence using the protocol. The intervention group had less median weight loss at discharge (-1.4 [0.1 to -4.3] kg) than usual care (-3.6 [-1.3 to 8.4] kg; p < 0.011), but no differences in malnutrition status were observed. CONCLUSION: A VBF protocol delivered greater EN volume, energy and protein following neurological injury. The VBF protocol was feasible with high acceptability from nursing staff.

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Glucose is the primary energy source for neural stem cells (NSCs), supporting their proliferation, differentiation, and quiescence. However, the high demand for glucose during brain development often exceeds its supply, leading to the utilization of alternative energy sources including ketone bodies. Ketone bodies, including ß-hydroxybutyrate, are short-chain fatty acids produced through hepatic ketogenesis and play a crucial role in providing energy and the biosynthetic components for NSCs when required. The interplay between glucose and ketone metabolism influences NSC behavior and fate decisions, and disruptions in these metabolic pathways have been linked to neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Additionally, ketone bodies exert neuroprotective effects on NSCs and modulate cellular responses to oxidative stress, energy maintenance, deacetylation, and inflammation. As such, understanding the interdependence of glucose and ketone metabolism in NSCs is crucial to understanding their roles in NSC function and their implications for neurological conditions. This article reviews the mechanisms of glucose and ketone utilization in NSCs, their impact on NSC function, and the therapeutic potential of targeting these metabolic pathways in neurological disorders.

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BACKGROUND: The prevalence of depression in Multiple Sclerosis (MS) is often assessed by administering patient reported outcome measures (PROMs) examining depressive symptomatology to population cohorts; a recent review summarised 12 such studies, eight of which used the Hospital Anxiety and Depression Scale-Depression (HADS-D). In clinical practice, depression is diagnosed by an individual structured clinical interview; diagnosis often leads to treatment options including antidepressant medication. It follows that an MS population will include those whose current depressive symptoms meet threshold for depression diagnosis, plus those who previously met diagnostic criteria for depression and have been treated such that depressive symptoms have improved below that threshold. We examined a large MS population to establish a multi-attribute estimate of depression, taking into account probable depression on HADS-D, as well as anti-depressant medication use and co-morbidity data reporting current treatment for depression. We then studied associations with demographic and health status measures and the trajectories of depressive symptoms over time. METHODS: Participants were recruited into the UK-wide Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study, with demographic and disease data from clinical records, PROMs collected at intervals of at least 9 months, as well as co-morbidities and medication. Interval level conversions of PROM data followed Rasch analysis. Logistic regression examined associations of demographic characteristics and symptoms with depression. Finally, a group-based trajectory model was applied to those with depression. RESULTS: Baseline data in 5633 participants showed the prevalence of depression to be 25.3 % (CI: 24.2-26.5). There were significant differences in prevalence by MS subtype: relapsing 23.2 % (CI: 21.8- 24.5), primary progressive 25.8 % (CI: 22.5-29.3), secondary progressive 31.5 % (CI: 29.0-34.0); disability: EDSS 0-4 19.2 % (CI: 17.8-20.6), EDSS ≥4.5 31.9 % (CI: 30.2-33.6); and age: 42-57 years 27.7 % (CI: 26.0-29.3), above or below this range 23.1 % (CI: 21.6-24.7). Fatigue, disability, self-efficacy and self esteem correlated with depression with a large effect size (>0.8) whereas sleep, spasticity pain, vision and bladder had an effect size >0.5. The logistic regression model (N = 4938) correctly classified 80 % with 93 % specificity: risk of depression was increased with disability, fatigue, anxiety, more comorbidities or current smoking. Higher self-efficacy or self esteem and marriage reduced depression. Trajectory analysis of depressive symptoms over 40 months in those with depression (N = 1096) showed three groups: 19.1 % with low symptoms, 49.2 % with greater symptoms between the threshold of possible and probable depression, and 31.7 % with high depressive symptoms. 29.9 % (CI: 27.6-32.3) of depressed subjects were untreated, conversely of those treated, 26.1 % still had a symptom level consistent with a probable case (CI: 23.5-28.9). CONCLUSION: A multi-attribute estimate of depression in MS is essential because using only screening questionnaires, diagnoses or antidepressant medication all under-estimate the true prevalence. Depression affects 25.3 % of those with MS, almost half of those with depression were either untreated or still had symptoms indicating probable depression despite treatment. Services for depression in MS must be pro-active and flexible, recognising the heterogeneity of outcomes and reaching out to those with ongoing symptoms.

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Intramedullary spinal cord metastasis (IMSC) from solid tumors is rare. In this report, we describe the case of a patient treated at our center for breast cancer with intramedullary spinal cord metastases without bone and brain metastases or meningitis. Management of the disease remains challenging even with recent advances in the treatment of metastatic breast cancer. Treatment options include surgery, radiotherapy and chemotherapy. The prognosis of these patients still very poor.

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Background: Digital Health technologies (DHT) have potential to deliver intensive, novel and engaging rehabilitation for people with neurological conditions, yet health services lack a strong track record in embedding DHT into practice. The aim of this review was to synthesise factors that have been shown to influence implementation of DHT into neurological rehabilitation. Method: An integrative review was undertaken. An extensive search of MEDLINE, CINAHL, AMED, EMBASE was undertaken. The title and abstract of all retrieved sources were screened against pre-defined criteria. Retained sources underwent full text review. The quality of all included sources was assessed. A meta-ethnographic synthesis explored commonalities and contradictions of the included studies. Results: Fourteen studies (1 quantitative, 8 qualitative and 5 mixed methods) were included. Eleven implementation theories/models/frameworks were used across the 14 studies. Five themes were identified: (i) individual factors; (ii) user experience of the technology; (iii) the content of the intervention; (iv) access to the technology and (v) supporting use. Conclusions: Key factors which appear to influence the implementation of DHT into clinical settings are highlighted. Implementation theories, models and frameworks are under-utilised in DHT rehabilitation research. This needs to be addressed if DHT are to realise their potential in neurological rehabilitation. Registration: The protocol was registered and is available from PROSPERO (CRD42021268984).

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The relentless pursuit of precision medicine has catalyzed the development of molecular and cellular tethered drug delivery systems, a burgeoning field that stands to redefine the paradigms of therapeutic delivery. This review encapsulates the cutting-edge advancements within this domain, emphasizing the engineering of molecular tethers and cellular vectors designed to ferry therapeutics directly to their target sites with unparalleled specificity and efficiency. By exploiting the unique biochemical signatures of disease states, these systems promise a substantial reduction in off-target effects and an enhancement in drug bioavailability, thereby mitigating the systemic side effects that are often associated with conventional drug therapies. Through a synthesis of recent research findings, this review highlights the innovative approaches being explored in the design and application of these tethered systems, ranging from nanotechnology-based solutions to genetically engineered cellular carriers. The potential of these systems to provide targeted therapy for a wide array of diseases, including cancer, autoimmune disorders, and neurological conditions, is thoroughly examined. This abstract aims to provide a succinct overview of the current state and future prospects of molecular and cellular tethered drug delivery systems in advancing the frontiers of precision medicine.

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Children and youth with neurological and/or neurodevelopmental conditions were at high risk for behavioral and mental health challenges during the COVID-19 pandemic. Positive and responsive parenting practices may be one way to prevent and manage potential difficulties in families. We aimed to identify whether positive parenting practices were associated with reduced behavioral concerns in children at neurological risk during the late stages and aftermath of the COVID-19 pandemic. In addition, we examined whether ongoing parental stress, anxiety, and depression impacted parenting practices during this time period. Families (N = 179) with children 4 to 15 years old (M = 7.11y, SD = 2.02) diagnosed with neurological (84.3%), neurodevelopmental (54.8%) or comorbid neurological and/or neurodevelopmental conditions (21.2%) were contacted to complete online questionnaires regarding demographics, parent stress, child behavior, COVID-19 conditions, and parenting practices. Multivariable linear regression (MLR) analyses examined the association between positive parenting practices and parenting competency measures with child behavioral outcomes, controlling for relevant covariates, including COVID-19 related stress. MLR were also run to determine whether parental mental health impacted parenting practices. More positive parenting practices predicted fewer child problem behaviors and lower intensity of problem behaviors. Similarly, a higher sense of satisfaction with parenting competence also predicted fewer child problem behaviors and lower intensity of problem behaviors. In addition, higher reported parental depression, anxiety, and stress significantly predicted fewer reported positive parenting practices. Findings points to the promising application of positive parenting interventions to support vulnerable families, as well as the need for parental mental health intervention to support parenting practices.

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PURPOSE: Community neurorehabilitation enables people with progressive neurological conditions (PNCs) to manage their symptoms to live an active, fulfilling life; however, it is not accessible to all. This study explored the factors influencing access to community neurorehabilitation in Northern Ireland from the perspective of people with PNCs and their carers. METHODS: Eleven people living with a PNC and three carers took part in virtual focus groups. Data was thematically analysed using the framework method. RESULTS: Access to neurorehabilitation was described as a staged journey, driven by people with PNCs, and impacted by interactions with others. Four themes were identified: the person in the driving seat, describing the value of person-centred care and the need for proactivity; the traffic lights, depicting the role and influence of health care professionals (HCPs); the need for direction; and roadworks and roadblocks, identifying additional barriers to access. In addition, six fundamentals of good access were identified. CONCLUSIONS: This study adds depth to our understanding of the complexity, and the roles and needs of people with PNCs and HCPs, in accessing community neurorehabilitation. Further research is needed to determine how best to empower people to access rehabilitation.

Access to community neurorehabilitation is dependent on personal factors including patient activation level and health care professional knowledge.People need to be empowered to access rehabilitation services.A single point of contact for advice and triaging concerns related to progressive neurological conditions is desirable.There is a need to understand the experiences and needs of people with low levels of patient activation to ensure equitable access to community-based neurorehabilitation.

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BACKGROUND: Precise prognostic information, if available, is very helpful for guiding treatment decisions and resource allocation in patients with non-cancer non-communicable chronic diseases (NCDs). This study aimed to systematically review the existing evidence, examining prognostic models and factors for identifying end-of-life non-cancer NCD patients. METHODS: Electronic databases, including Medline, Embase, CINAHL, Cochrane Library, PsychINFO and other sources, were searched from the inception of these databases up until June 2023. Studies published in English with findings mentioning prognostic models or factors related to identifying end-of-life in non-cancer NCD patients were included. The quality of studies was assessed using the Quality in Prognosis Studies tool. RESULTS: The analysis included data from 41 studies, with 16 focusing on chronic obstructive pulmonary diseases (COPD), 10 on dementia, 6 on heart failure and 9 on mixed NCDs. Traditional statistical modelling was predominantly used for the identified prognostic models. Common predictors in COPD models included dyspnoea, forced expiratory volume in 1 s, functional status, exacerbation history and body mass index. Models for dementia and heart failure frequently included comorbidity, age, gender, blood tests and nutritional status. Similarly, mixed NCD models commonly included functional status, age, dyspnoea, the presence of skin pressure ulcers, oral intake and level of consciousness. The identified prognostic models exhibited varying predictive accuracy, with the majority demonstrating weak to moderate discriminatory performance (area under the curve: 0.5-0.8). Additionally, most of these models lacked independent external validation, and only a few underwent internal validation. CONCLUSION: Our review summarised the most relevant predictors for identifying end-of-life in non-cancer NCDs. However, the predictive accuracy of identified models was generally inconsistent and low, and lacked external validation. Although efforts to improve these prognostic models should continue, clinicians should recognise the possibility that disease heterogeneity may limit the utility of these models for individual prognostication; they may be more useful for population level health planning.

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PURPOSE: Self-awareness is a multifaceted phenomenon that comprises two main concepts: general awareness and online awareness. The latter is an emerging concept that requires further consensus on its definition. The aim of this paper is to define the key components of online awareness and identify approaches for measuring this concept for adults with neurological conditions. MATERIALS AND METHODS: Concept analysis using Rodgers' evolutionary method was used to systematically review and summarise relevant literature. Papers were included if they provided a definition of online awareness or method for assessing online awareness for an adult neurological population. RESULTS: Fifty-six papers were included in this review, with 21 online awareness assessment approaches identified. Online awareness was described to occur within the context of task performance, with the definition framework comprising four main aspects: 1/appraisal; 2/anticipation and prediction; 3/monitoring; and 4/self-evaluation. Self-regulation is a related concept that is considered to sit outside the conceptual boundaries of online awareness. CONCLUSIONS: The findings of this analysis highlight the complexity of online awareness and its importance in rehabilitation. Psychometrically robust measures of online awareness that are inclusive of the essential elements of this concept are needed to advance practice in this area.

Online awareness or awareness of performance within the context of an activity should be included in the comprehensive assessment of self-awareness for individuals with neurological conditions.Online awareness is a task-specific phenomenon that is activated in the context of task performance, and requires assessment across a range of tasks and environments.When assessing online awareness, careful consideration is required when selecting tasks to ensure they have the right level of challenge to elicit the need to monitor performance.The heterogeneity of existing online awareness assessments highlights the need to interpret outcomes with caution.Future efforts should be directed towards development of an online awareness assessment that includes key attributes of this concept.