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Introduction: There is a growing emphasis on the importance of the availability of specialist palliative care for people with motor neuron disease (MND). However, the palliative care needs of this population and the utilisation of different specialist services remain poorly defined., Objectives: To (1) describe clinical characteristics, symptom burden and functional levels of patients dying with MND on their admission to palliative care services; (2) determine factors associated with receiving inpatient or community palliative care services., Design: An observational study based on point-of-care assessment data from the Australian Palliative Care Outcomes Collaboration., Participants: A total of 1308 patients who received palliative care principally because of MND between 1 January 2013 and 31 December 2020., Measures: Five validated clinical instruments were used to assess each individual's function, distress from symptoms, symptom severity and urgency and acuity of their condition., Results: Most patients with MND had no or mild symptom distress, but experienced a high degree of functional impairment. Patients who required 'two assistants for full care' relative to those who were 'independent' (OR=11.53, 95% CI: 4.87 to 27.26) and those in 'unstable' relative to 'stable' palliative care phases (OR=16.74, 95% CI: 7.73 to 36.24) were more likely to use inpatient versus community-based palliative care. Associations between the use of different palliative care services and levels of symptom distress were not observed in this study., Conclusions: Patients with MND were more likely to need assistance for decreased function and activities of daily living, rather than symptom management. This population could have potentially been cared for in the palliative phase in a community setting if greater access to supportive services were available in this context., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Given the degenerative nature of the condition, people living with motor neuron disease (MND) experience high levels of psychological distress. The purpose of this research was to investigate the cost-effectiveness of acceptance and commitment therapy (ACT), adapted for the specific needs of this population, for improving quality of life., Methods: A trial-based cost-utility analysis over a 9-month period was conducted comparing ACT plus usual care (n = 97) versus usual care alone (n = 94) from the perspective of the National Health Service. In the primary analysis, quality-adjusted life years (QALYs) were computed using health utilities generated from the EQ-5D-5L questionnaire. Sensitivity analyses and subgroup analyses were also carried out., Results: Difference in costs was statistically significant between the two arms, driven mainly by the intervention costs. Effects measured by EQ-5D-5L were not statistically significantly different between the two arms. The incremental cost-effectiveness was above the £20,000 to £30,000 per QALY gained threshold used in the UK. However, the difference in effects was statistically significant when measured by the McGill Quality of Life-Revised (MQOL-R) questionnaire. The intervention was cost-effective in a subgroup experiencing medium deterioration in motor neuron symptoms., Conclusions: Despite the intervention being cost-ineffective in the primary analysis, the significant difference in the effects measured by MQOL-R, the low costs of the intervention, the results in the subgroup analysis, and the fact that ACT was shown to improve the quality of life for people living with MND, suggest that ACT could be incorporated into MND clinical services., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: When commencing enteral feeding, patients and families will want to know the likelihood of returning to an oral diet. There is a paucity of data on the prognosis of patients with gastrostomies. We describe a large dataset of patients, which identifies factors influencing gastrostomy removal and assesses the likelihood of the patient having at home enteral nutrition., Methods: Retrospective data was collected on patients from Sheffield Teaching Hospitals who had received a gastrostomy and had outpatient enteral feeding between January 2016 and December 2019. Demographic data, indication and outcomes were analysed., Results: A total of 451 patients were assessed, median age: 67.7. 183/451(40.6%) gastrostomies were for head and neck cancer, 88/451 (19.5%) for stroke, 28/451 (6.2%) for Motor Neuron Disease, 32/451 (7.1%) for other neurodegenerative causes, 120/451 (26.6%) other. Of the 31.2% who had their gastrostomy removed within 3 years, head and neck cancer was the most common indication (58.3%) followed by stroke (10.2%), Motor Neuron Disease (7.1%) and other neurodegenerative diseases (3.1%). Gastrostomy removal was significantly influenced by age, place of residence, and having head and neck cancer ( p  < 0.05). There was the greatest likelihood of removal within the first year (24%). 70.5% had enteral feeding at home., Conclusion: This large cohort study demonstrates 31.2% of patients had their gastrostomy removed within 3 years. Head and neck cancer patients, younger age and residing at home can help positively predict removal. Most patients manage their feeding at home rather than a nursing home. This study provides new information on gastrostomy outcomes when counselling patients to provide realistic expectations.

Objective: MiNDToolkit is a novel psychoeducational intervention for carers to support management of behavioral symptoms in people living with motor neuron disease (PlwMND). Implementation of MiNDToolkit involves delivery of an online intervention to carers, which is reinforced by trained healthcare professionals (HCPs)., Methods: A mixed-methods process evaluation of the MiNDToolkit feasibility trial was conducted, focusing on reinforcement of the intervention by HCPs. Quantitative data, descriptively analyzed, were included from platform analytics, questionnaire, and 10 semi-structured interviews with HCPs. Interviews were transcribed verbatim; data were inductively analyzed using Reflective Thematic Analysis., Results: The MiNDToolkit training and platform is a beneficial and acceptable resource for HCPs with potential to increase knowledge and confidence in identifying and managing behavioral symptoms in MND. Implementation barriers included HCPs' perceptions that highlighting behavior changes would be burdensome to carers and assumptions that carers would take the initiative to ask for support from clinicians. Degree of intervention reinforcement varied, with most HCPs delegating intervention delivery solely to the online platform., Conclusions: Implementation of the MiNDToolkit was viewed to be feasible and the platform thought to increase accessibility of support to carers. The flexible approach to delivery (online platform and optional HCP reinforcement) is acceptable as an intervention for supporting carers of PlwMND with behavioral symptoms. However, MiNDToolkit should not negate HCP involvement in providing medical and practical information to PlwMND and families. Future research should explore ways to incorporate support for carers in the management of PlwMND alongside standard care, alongside tools such as the MiNDToolkit.

Background: Evidence on management of behavioral symptoms in motor neuron disease (MND) is lacking. The MiNDToolkit, an online psychoeducational platform, supports carers dealing with behavioral symptoms (BehSymp). The study objectives were to ascertain recruitment and retention rates, carer and healthcare professional (HCP) use of the platform, and completion of online assessments, to inform a full-scale trial. Design : Randomized, parallel, multi-center, feasibility trial., Setting: England and Wales, across diverse MND services; recruitment from July/21 to November/22; last participant follow-up in March/23., Participants: Carers of people with motor neuron disease (PwMND) with BehSymp, recruited through MND services. After confirming eligibility, participants completed screening and baseline assessments online via the MiNDToolkit platform and were randomized centrally in a 1:1 ratio to MiNDToolkit or control., Intervention: MiNDToolkit offered tailored modules to carers for the 3-month study period. Carers in the intervention group could receive additional support from MiNDToolkit trained HCPs. The control group was offered access to the intervention at the end of the study. Data were collected on platform usage and psychosocial variables., Main Outcomes: One hundred and fifty-one carers from 11 sites were invited to join the study (letter, face-to-face); 30 were screened; 29 were randomized. Fifteen people were allocated to the control arm; 14 to intervention. Carers were mostly female; median age for was 62.5 (IQR: 58, 68; intervention) and 57 (IQR: 56, 70; controls). Study retention was high (24/29 = 82.76%); carers engaged with the platform on average 14 times (median (IQR):14.0 (10.0, 18.5)) during the study period., Conclusion: The MiNDToolkit study was feasible and well accepted by carers and trained HCPs. A definitive trial is warranted.

Background: To explore carers' experiences of behavioural symptoms in Motor Neurone Disease (MND), before and after using the MiNDToolkit, a novel internet-based psychoeducational intervention to support management of behavioural symptoms (BehSymp) in MND. The study also investigated carers' views and acceptability of MiNDToolkit., Methods: A qualitative process evaluation of carers engagement with, and acceptability of, the MiNDToolkit conducted using semi-structured interviews with carers (n = 11). All interviews were audio-recorded, professionally transcribed verbatim and analysed thematically., Results: Five themes were identified: (1) In the dark: carers' experiences and reactions to BehSymp; (2) Others can see: the role of HCPs in identifying symptoms - and perceived opportunities for carers to receive support; (3) Shedding light: carers implementation and perceived impact of the MiNDToolkit content; (4) Acceptability and carers' engagement with MiNDToolkit; (5) Future implementation. Carers' experience of BehSymp was particularly distressing when symptoms were apparently out of context. MiNDToolkit appeared to support learning that BehSymp were part of MND. Content resonated with carers, who reported learning about the full picture of MND, which led to acceptance and use of newly learned strategies. Engagement with the platform was good, with varied input from HCPs. Greater and nuanced involvement from HCPs seem important to support management of BehSymp. Recommendations for a full-scale trial emerged, including adding a paper booklet to accompany the intervention and creation of new modules on emotional lability, changes in relationships, and transitioning to a care home., Conclusions: MiNDToolkit was acceptable to carers overall. Recommended improvements should be actioned in a full-scale trial., (© 2024. The Author(s).)

Motor neuron disease (MND) is an uncommon but invariably fatal condition, with a median survival of 24-48 months from symptom onset. Although there is no cure at the moment, early diagnosis is crucial to enable timely access to multidisciplinary care, and enrolment in clinical trials utilising investigational therapies. Unfortunately, diagnostic delays remain common, and the average delay between symptom onset and diagnosis is 12 months. Large numbers of specialist referrals have been suggested as a key contributor to diagnostic delays. We conducted a retrospective review of the medical records of patients diagnosed with MND in Lancashire and South Cumbria, to investigate whether large numbers of specialty referrals are a common occurrence in MND. Our review identified that 35% of patients with MND were seen by two or more specialties before being referred to neurology. This rose to 49% when patients with bulbar onset disease were considered. 9% of cases saw three or more specialists. There was a statistically significant correlation between the number of specialist referrals and delays in neurology referral. We hope our findings will increase awareness of the importance of early neurology referral in the diagnosis of MND and promote the use of the MND Red Flag tool as a means of identifying patients in need of prompt neurological evaluation., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interests., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Background: Tracheostomy ventilation in motor neurone disease is an uncommon life-sustaining treatment. Best practice is having a plan for ventilation withdrawal, but the literature to guide practice is limited. Case reports have documented standard doses of opioids and benzodiazepines used for sedation in such cases., Case: A 49-year-old man was diagnosed with motor neurone disease in 2016. He commenced tracheostomy ventilation in 2018. In 2022 and 2023, planning was undertaken, at the patient's request, for withdrawal of tracheostomy ventilation at home, when he was no longer able to communicate with technology., Case Planning: Planning included Bispectral Index monitoring prior to cessation of ventilation, ensuring this only occurred when deep sedation was achieved. After ventilation withdrawal in 2023, a retrospective review of medications given and his level of sedation on monitoring was undertaken, with family consent., Outcome: Ventilation withdrawal was initiated after deep sedation was achieved, 6 h after commencing subcutaneous infusions of morphine, midazolam, clonazepam and phenobarbital., Lessons: Doses required to achieve acceptable sedation exceeded literature reports. Achieving deep sedation was a longer than expected process., Conclusion: More research using an objective measure of sedation is required, as clinical assessment of sedation in this context is compromised., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: Data on care home admission and survival rates of patients with syndromes associated with frontotemporal lobar degeneration (FTLD) are limited. However, their estimation is essential to plan trials and assess the efficacy of intervention. Population-based registers provide unique samples for this estimate. The aim of this study was to assess care home admission rate, survival rate, and their predictors in incident patients with FTLD-associated syndromes from the European FRONTIERS register-based study., Methods: We conducted a prospective longitudinal multinational observational registry study, considering incident patients with FTLD-associated syndromes diagnosed between June 1, 2018, and May 31, 2019, and followed for up to 5 years till May 31, 2023. We enrolled patients fulfilling diagnosis of the behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS), and FTD with motor neuron disease (FTD-MND). Kaplan-Meier analysis and Cox multivariable regression models were used to assess care home admission and survival rates. The survival probability score (SPS) was computed based on independent predictors of survivorship., Results: A total of 266 incident patients with FTLD were included (mean age ± SD = 66.7 ± 9.0; female = 41.4%). The median care home admission rate was 97 months (95% CIs 86-98) from disease onset and 57 months (95% CIs 56-58) from diagnosis. The median survival was 90 months (95% CIs 77-97) from disease onset and 49 months (95% CIs 44-58) from diagnosis. Survival from diagnosis was shorter in FTD-MND (hazard ratio [HR] 4.59, 95% CIs 2.49-8.76, p < 0.001) and PSP/CBS (HR 1.56, 95% CIs 1.01-2.42, p = 0.044) compared with bvFTD; no differences between PPA and bvFTD were found. The SPS proved high accuracy in predicting 1-year survival probability (area under the receiver operating characteristic curve = 0.789, 95% CIs 0.69-0.87), when defined by age, European area of residency, extrapyramidal symptoms, and MND at diagnosis., Discussion: In FTLD-associated syndromes, survival rates differ according to clinical features and geography. The SPS was able to predict prognosis at individual patient level with an accuracy of ∼80% and may help to improve patient stratification in clinical trials. Future confirmatory studies considering different populations are needed.

Background: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease., Methods: We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391)., Findings: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22-1·10]; d=0·46 [0·16-0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention., Interpretation: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services., Funding: National Institute for Health and Care Research Health Technology Assessment and Motor Neurone Disease Association., Competing Interests: Declaration of interests RLG, CJM, BJT, CVR, MBu, MBr, PK, EJT, DAW, MAS, CDG, LMM, LHG, AA-C, TY, VL, CC, PJS, and RJH declare institutional financial support from the grant for the submitted work (National Institute for Health and Care Research Health Technology Assessment 16/81/01). RLG, MAS, RJH, MBr, CC, TY, PJS, CJM, AA-C, VL, and LHG are supported by a public research body (National Institute for Health and Care Research Biomedical Research Centres). LHG has received royalties for books on psychology and neuropsychology and fees for lectures on neurology. AA-C and PJS receive payment for consultancy and advisory board participation from commercial organisations (Amylyx, Apellis, Biogen, Brainstorm, Clene Therapeutics, Cytokinetics, GenieUs, GSK, Lilly, Mitsubishi Tanabe Pharma, Novartis, OrionPharma, Quralis, Sano, Sanofi, and Wave Pharmaceuticals), none of which are related to the content of this submitted work. RWO, LMM, and CF have received grants for research from public bodies. RWO has received grants for research and trials from commercial organisations (Amylyx Pharmaceuticals, Biogen, Orphazyme) and received payment for neurological medicolegal work. RWO and CF sit on safety monitoring or advisory boards for motor neuron disease. RWO, JE, and AH sit on boards in organisations associated with motor neuron disease. AH receives grant funding for his clinical role at Motor Neurone Disease Association. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: I report consulting fees from Amylyx, Biogen, Roche, Zambon, ITF Pharma, and Ferrer.

Background: Motor Neurone Disease (MND) leads to muscle weakening, affecting movement, speech, and breathing. Home mechanical ventilation, particularly non-invasive ventilation (NIV), is used to alleviate symptoms and support breathing in people living with MND. While home mechanical ventilation can alleviate symptoms and improve survival, it does not slow the progression of MND. This study addresses gaps in understanding end-of-life decision-making in those dependent on home mechanical ventilation, considering the perspectives of patients, family members, and bereaved families., Methods: A UK-wide qualitative study using flexible interviews to explore the experiences of people living with MND (n = 16), their family members (n = 10), and bereaved family members (n = 36) about the use of home mechanical ventilation at the end of life., Results: Some participants expressed a reluctance to discuss end-of-life decisions, often framed as a desire to "live for the day" due to the considerable uncertainty faced by those with MND. Participants who avoided end-of-life discussions often engaged in 'selective decision-making' related to personal planning, involving practical and emotional preparations. Many faced challenges in hypothesising about future decisions given the unpredictability of the disease, opting to make 'timely decisions' as and when needed. For those who became dependent on ventilation and did not want to discuss end of life, decisions were often 'defaulted' to others, especially once capacity was lost. 'Proactive decisions', including advance care planning and withdrawal of treatment, were found to empower some patients, providing a sense of control over the timing of their death. A significant proportion lacked a clear understanding of the dying process and available options., Conclusions: The study highlights the complexity and evolution of decision-making, often influenced by the dynamic and uncertain nature of MND. The study emphasises the need for a nuanced understanding of decision-making in the context of MND., (© 2024. The Author(s).)

Background: Long-term neurological conditions include multiple sclerosis, Parkinson's-related diseases, and motor neurone disease. National and international guidelines recommend a palliative approach for advancing neurological disease, but there is little research describing and comparing the palliative care needs of these patients side by side. Objective: The aim of this study was to describe and compare the symptom burden and psychological distress of patients with multiple sclerosis, Parkinson's-related diseases, and motor neurone disease. Design: A cross-sectional secondary analysis of the OPTCARE Neuro trial data was performed. Setting/Subjects: Recruitment was from seven sites across the United Kingdom. Patients aged 18 years or older, severely affected by advanced stages of multiple sclerosis or Parkinson's-related diseases or any stage of motor neurone disease, with an unresolved symptom, and one other issue despite usual care were eligible. Measurements: Baseline demographics, Integrated Palliative care Outcome Scale (IPOS) Neuro, and Hospital Anxiety and Depression Scale (HADS) results were analyzed. Results: Data from 348 participants were analyzed. The mean IPOS Neuro-S24 score was 27, with no statistical difference found between groups ( p  = 0.341). The most common symptoms were poor mobility (68.5%), problems using legs (63%), and fatigue (34.8%). The HADS revealed that a quarter of participants met the criteria for a diagnosis of anxiety and depression. Conclusions: Multiple sclerosis, Parkinson's-related disease, and motor neurone disease patients who were eligible for the OPTCARE Neuro trial have unmet needs in the form of distressing physical and psychological symptoms. It is unclear how to address these needs. The answer likely lies in a collaborative approach between neurology, palliative care, psychology, and specialized allied health professionals. Future work should focus on investigating this.

Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins, and decrease levels of toxic proteins. ASOs are being developed for the treatment of motor neuron diseases (MNDs), including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MNDs, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.

Introduction/aims: Enteral feeding via gastrostomy is a key intervention to prevent significant weight loss in Motor Neuron Disease (MND). The aim of this study was to explore demographic, clinical, and nutritional factors associated with survival time in MND patients with gastrostomy., Methods: The retrospective study analyzed 94 MND patients (n = 58 bulbar-onset and n = 36 limb-onset) who underwent gastrostomy between 2015 and 2021. The primary outcome was the survival time from gastrostomy insertion to death. Independent variables of interest explored were: age at gastrostomy insertion, disease onset type, known genetic cause, use of riluzole, non-invasive ventilation (NIV) use, forced vital capacity prior to gastrostomy, weight loss from diagnosis to gastrostomy insertion, and body mass index (BMI) at the time of gastrostomy insertion., Results: The median survival time from gastrostomy to death was 357 days (± 29.3, 95%CI: 299.5, 414.5). Kaplan-Meier method and log-rank test revealed patients with lower body mass index <18.5 kg/m 2 at the time of gastrostomy insertion (p = .023) had shorter survival. Cox proportional hazards model with multivariable adjustment revealed that older age (p = .008), and greater weight loss from diagnosis to gastrostomy (p = .003) were associated with shorter survival time post gastrostomy. Limb onset (p = .023), NIV use not being required (p = .008) and daily NIV use when required and tolerated (p = .033) were associated with longer survival., Discussion: Preventing or minimizing weight loss from MND diagnosis and encouraging NIV use when clinically indicated are modifiable factors that may prolong the survival of MND patients with gastrostomy., (© 2024 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Palliative care (PC) defined as 'an approach improving the quality of life of patients and their families facing problems associated with life-limiting illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual' aims to enhance the improve the remaining time that patients have, emphasising choice for patients and families. 1 Patients with neurological disease such as Parkinson's (PD) and motor neurone disease (MND) benefit from PC earlier in disease with increasing emphasis over time. Understanding and communicating uncertain trajectories, honest prognostic communication when patients are ready and careful symptom control has been shown to enhance quality of life in patients and caregivers, giving greater autonomy to these patients when supported in decision-making by a palliative approach. Although obstacles to palliative care are frequent, there are strategies which can help overcome them., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Non-invasive brain stimulation techniques have been exploited in motor neuron disease (MND) with multifold objectives: to support the diagnosis, to get insights in the pathophysiology of these disorders and, more recently, to slow down disease progression. In this review, we consider how neuromodulation can now be employed to treat MND, with specific attention to amyotrophic lateral sclerosis (ALS), the most common form with upper motoneuron (UMN) involvement, taking into account electrophysiological abnormalities revealed by human and animal studies that can be targeted by neuromodulation techniques. This review article encompasses repetitive transcranial magnetic stimulation methods (including low-frequency, high-frequency, and pattern stimulation paradigms), transcranial direct current stimulation as well as experimental findings with the newer approach of trans-spinal direct current stimulation. We also survey and discuss the trials that have been performed, and future perspectives., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The purpose of this mixed methods systematic review was to identify factors associated with anticipatory grief, post-death grief, and prolonged grief in informal carers of people living with Motor Neuron Disease (MND) to inform future research and practice. Six electronic databases were searched and two quantitative and eight qualitative studies were identified. Five overarching themes were generated through thematic synthesis. The findings suggest that there are factors that may affect different grieving processes. It might be particularly important to target some factors prior and after the death of the person living with MND such as the knowledge about the progression of the disease, changes in relationships, anxiety and depressive symptoms of carers, and planning for death of the care recipient. Factors that may affect all three grieving processes were also identified such as negative experiences of caregiving, experiences of losses, end of life and psychological support, and emotional avoidance coping.

Background: There is a need for knowledge regarding the medical management of motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) with and without cognitive decline. It has scarcely been studied whether cognitive decline will influence the course of disease or interfere with the use of life-prolonging aids for respiration and nutrition. Cognitive decline may impact the length of illness., Methods: Patients were prospectively recruited from an ALS outpatient clinic at Haukeland University Hospital. Participants underwent the standardized cognitive test Edinburgh Cognitive and Behavioral ALS Screen Norwegian version (ECAS-N), clinical examination, and were functionally assessed by the ALS Functioning Rating Scale-revised version (ALS-FRS-R). The time and indication for installation of a feeding tube [percutaneous endoscopic gastrostomy (PEG)] and/or respiratory aid [bilevel positive airway pressure device (BiPAP)] or invasive respirator were retrieved from the medical records. Kaplan-Meier tests were used to study the risk of death and the probability for implementing PEG and/or BiPAP in relation to time from diagnosis. The individual assessment was used for analyzing the establishment of aids in relation to point of death., Results: A total of 40 patients were evaluated for the study, 31 of whom were finally included. None of the included patients did not use an invasive respirator. The patients were divided into two subgroups (normal cognition or cognitive decline, cut-off 92 points) according to their performance in the ECAS-N. The course of the disease, shown as a risk of death, was higher among the ALS/MND patients with cognitive decline compared to those with cognitive intact function throughout the study period. The cognitive status did not influence the fitting of aids. Use of aids did not influence the survival in subgroups significantly., Conclusions: The study demonstrated shorter survival for the patients with ALS/MND with cognitive decline compared to those without cognitive decline. The practice and implementation of both BiPAP and PEG did not differ among the ALS/MND patients with and without cognitive decline in Norway.

The aim of supportive management of motor neuron disease is to improve survival, promote good quality of life and patient independence and autonomy whilst preparing for future progression and the end of life. Multidisciplinary specialist care aims to address the multifaceted and interacting biopsychosocial problems associated with motor neuron disease that leads to proven benefits in both survival and quality of life. This chapter will explore principles, structure and details of treatment options, and make recommendations for practice and for future research., (Copyright © 2024. Published by Elsevier Inc.)

Motor neuron disease (MND) is a rapidly progressive neurodegenerative disorder with limited treatment options. Historically, neurological trials have been plagued by suboptimal recruitment and high rates of attrition. The Motor Neuron Disease-Systematic Multi-Arm Randomised Adaptive Trial (MND-SMART) seeks to identify effective disease modifying drugs. This study investigates person-specific factors affecting recruitment and retention. Improved understanding of these factors may improve trial protocol design, optimise recruitment and retention. Participants with MND completed questionnaires and this was supplemented with clinical data. 12 months after completing the questionnaires we used MND-SMART recruitment data to establish if members of our cohort engaged with the trial. 120 people with MND completed questionnaires for this study. Mean age at participation was 66 (SD = 9), 14% (n = 17) were categorised as long survivors, with 68% (n = 81) of participants male and 60% (n = 73) had the ALS sub-type. Of the 120 study participants, 50% (n = 60) were randomised into MND-SMART and 78% (n = 94) expressed interest an in participating. After the 1-year follow-up period 65% (n = 39) of the 60 randomised participants remained in MND-SMART. Older age was significantly associated with reduced likelihood of participation (OR = 0.92, 95% CI = 0.88-0.96, p = 0.000488). The findings show that people with MND are highly motivated to engage in research, but older individuals remain significantly less likely to participate. We recommend the inclusion of studies to explore characteristics of prospective and current participants alongside trials., (© 2023. The Author(s).)

A common feature of adult-onset neurodegenerative diseases is the presence of characteristic pathological accumulations of specific proteins. These pathological protein depositions can vary in their protein composition, cell-type distribution, and intracellular (or extracellular) location. For example, abnormal cytoplasmic protein deposits which consist of the TDP-43 protein are found within motor neurons in patients with amyotrophic lateral sclerosis (ALS, a common form of motor neuron disease) and frontotemporal dementia (FTD). The presence of these insoluble intracellular TDP-43 inclusions suggests that restoring TDP-43 homeostasis represents a potential therapeutical strategy, which has been demonstrated in alleviating neurodegenerative symptoms in cell and animal models of ALS/FTD. We have reviewed the mechanisms that lead to disrupted TDP-43 homeostasis and discussed how small molecule-based therapies could be applied in modulating these mechanisms. This review covers recent advancements and challenges in small molecule-based therapies that could be used to clear pathological forms of TDP-43 through various protein homeostasis mechanisms and advance the way towards finding effective therapeutical drug discoveries for neurodegenerative diseases characterized by TDP-43 proteinopathies, especially ALS and FTD. We also consider the wider insight of these therapeutic strategies for other neurodegenerative diseases., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Motor neurone disease is a rare but debilitating illness with incomplete evidence regarding patients' symptom burden. Palliative care and generalist clinicians are often in-experienced in caring for these patients and assessing their needs., Aim: To identify the symptom prevalence and severity experienced by patients with motor neurone disease. Secondary objectives were to examine differences in symptom burden and clusters according to phenotype, functional status, palliative care provision and those in their last months of life., Design: A point prevalence study assessing patient-reported symptoms using a modified IPOS-Neuro assessment tool, incorporating 41 symptom items., Setting/participants: Patients with motor neurone disease attending the State-wide Progressive Neurological Disease Service or inpatient unit at Calvary Health Care Bethlehem, Melbourne Australia, from March to December 2021., Results: A total of 102 patients participated, the majority diagnosed with lumber-onset (30.4%), bulbar-onset (28.4%) and cervical-onset (25.5%) phenotypes. Patients experienced a median of 17 symptoms (range 2-32) with a median of 3 symptoms rated as severe/overwhelming (range 0-13). Motor and functional symptoms predominated, with differences in symptom clusters present according to phenotype. Patients had a higher number of severe/overwhelming symptoms if they were accessing palliative care services ( p  = 0.005), in their last 6 months of life ( p  = 0.003) and experiencing moderate or severe functional impairment ( p  < 0.001)., Conclusions: Patients with motor neurone disease report high symptom burden. A validated motor neurone disease-specific symptom assessment tool is needed to accurately assess patients, including important variations in symptom clusters according to phenotype. Further research must focus on evidence-based treatment guidelines for symptoms experienced commonly and severely., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This article reviews the clinical spectrum of amyotrophic lateral sclerosis (ALS), its variant presentations, and the approach to diagnosis and management. This review includes a detailed discussion of current and emerging disease-modifying therapies and the management of respiratory and bulbar manifestations of disease. An updated review of ALS genetics and pathophysiology is also provided. This article also touches on several other important motor neuron diseases., Latest Developments: A new set of simplified diagnostic criteria may help identify patients at earlier stages of the disease. A coformulation of sodium phenylbutyrate and tauroursodeoxycholic acid has been shown to have a significant benefit on disease progression and survival, leading to approval by regulatory authorities in the United States and Canada. An oral formulation of edaravone and an antisense oligonucleotide to a SOD1 gene variation (tofersen) have also recently been approved by the US Food and Drug Administration (FDA). Phase 3 trials of intrathecal mesenchymal stem cells failed to meet primary end points for efficacy. Updated American Academy of Neurology quality measures for the care of patients with ALS were published in 2023., Essential Points: There has been continued progress in ALS genetics, diagnosis, and disease-modifying therapies. However, we still lack a definitive biomarker or a treatment that can halt the progression or reverse the course of disease. The evolving understanding of the genetic and pathophysiologic underpinnings of disease offers promise for more effective and clinically meaningful treatments in the future., (Copyright © 2023 American Academy of Neurology.)

NICE (National Institute for Health & Care Excellence) guidance recommends that healthcare professionals with expertise in palliative care should be an integral part of the multidisciplinary team in managing patients with motor neuron disease (MND). Those in the poorest prognostic group may benefit from early referral to help manage rapidly progressive symptoms, psychological distress and offer additional support with complex decision-making and early robust advance care planning. Patients frequently develop dysphagia and gastrostomy feeding can be used to prolong survival and improve quality of life. As the disease progresses patients may request withdrawal of life-sustaining treatment such as gastrostomy feeding; however, a literature search found no evidence or guidance on how best to facilitate this. We present the case of a patient with MND admitted to the hospice inpatient unit requesting withdrawal of gastrostomy feeding, outline the challenges and need for further consensus guidelines to inform practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: People with motor neuron disease (pwMND) are routinely offered gastrostomy feeding tube placement and (non-invasive and invasive) ventilation to manage the functional decline associated with the disease. This study aimed to synthesise the findings from the qualitative literature to understand how individual, clinical team and organisational factors influence pwMND decisions about these interventions., Methods: The study design was guided by the enhancing transparency in reporting the synthesis of qualitative research (ENTREC) statement. The search of five bibliography databases and an extensive supplementary search strategy identified 27 papers that included qualitative accounts of pwMND, caregivers and healthcare professionals' (HCPs) experiences of making decisions about gastrostomy and ventilation. The findings from each study were included in a thematic synthesis., Findings: Making decisions about interventions is an emotional rather than simply a functional issue for pwMND. The interventions can signal an end to normality, and increasing dependence, where pwMND consider the balance between quality of life and extending survival. Interactions with multiple HCPs and caregivers can influence the process of decision-making and the decisions made. These interactions contribute to the autonomy pwMND are able to exert during decision-making. HCPs can both promote and threaten pwMND perceived agency over decisions through how they approach discussions about these interventions. Though there is uncertainty over the timing of interventions, pwMND who agree to interventions report reaching a tipping point where they accept the need for change., Conclusion: Discussion of gastrostomy and ventilation options generate an emotional response in pwMND. Decisions are the consequence of interactions with multiple external agents, including HCPs treading a complex ethical path when trying to improve health outcomes while respecting pwMND right to autonomy. Future decision support interventions that address the emotional response and seek to support autonomy have the potential to enable pwMND to make informed and timely decisions about gastrostomy placement and ventilation., Patient or Public Contribution: The lead author collaborated with several patient and participant involvement (PPI) groups with regards to the conceptualisation and design of this project. Decisions that have been influenced by discussions with multiple PPI panels include widening the scope of decisions about ventilation in addition to gastrostomy placement and the perceptions of all stakeholders involved (i.e., pwMND, caregivers and HCPs)., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Aims and Objectives: The overall aim of this paper is to provide practical insight into the way that professionals caring for a person with motor neurone disease (MND) can recognise, respect and respond to that person's temporality; that is, the person that they have been, that they are now and that they will be in the future., Background: MND is an umbrella term for a group of four rare, devastating neurodegenerative terminal diseases of middle/later life. Previously, we have acknowledged the importance of different time periods in the trajectory of MND as an illness, for example, during the diagnosis stage through to end of life and decision-making at that time. Living with MND can cause anxiety at all stages of the disease trajectory especially as it can be difficult for people living with MND to communicate their desires and concerns to professionals and carers. It is important that professionals continue to provide holistic care throughout the illness trajectory and the aim of this paper is to explore past research about caring for someone with MND in relation to the concept of person-centred care., Method: The paper is based on the concatenated exploration of the findings of a hermeneutic phenomenological project. Thus, this discursive paper links elements/studies which have been published previously to develop a model of person-centred care for people with MND which recognises and respects their temporality., Conclusions: We suggest MND has a significant impact on a person's lifeworld. The proposed person-centred care model focuses on understanding (interpreting) a person in a wider temporal frame and beyond the context of their illness. The expected collaborative outcomes are that: a person is acknowledged as more than a 'patient with MND' and that a professional is providing person-centred care based on individuality of the person, through a temporal lens. This requires a collaborative approach between the person, others and professionals. Such person-centred care, focused on individuality, may prevent a person experiencing life in crisis and suffering towards the end of life., (© 2023 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Motor Neuron Diseases (MND) are neurological disorders characterized by a loss of varying motor neurons resulting in decreased physical capabilities. Current research is focused on hindering disease progression by determining causes of motor neuron death. Metabolic malfunction has been proposed as a promising topic when targeting motor neuron loss. Alterations in metabolism have also been noted at the neuromuscular junction (NMJ) and skeletal muscle tissue, emphasizing the importance of a cohesive system. Finding metabolism changes consistent throughout both neurons and skeletal muscle tissue could pose as a target for therapeutic intervention. This review will focus on metabolic deficits reported in MNDs and propose potential therapeutic targets for future intervention.

Background: Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease. Besides a timely diagnosis, precise knowledge of the clinical manifestations and differential diagnoses is essential. While most patients develop the disease at an older age, hereditary causes play a more frequent role in the juvenile forms., Objective: What is the current state of ALS diagnostics, which new treatment options exist?, Material and Method: Literature search using Pubmed.gov., Results: The main focus is on an individualized symptomatic treatment as no curative treatment approaches exist. However, new insights into the genetic and pathophysiological principles of the different forms of ALS open the way for future disease-modifying treatment options., Conclusion: In cases of a clinical suspicion of ALS molecular genetic diagnostics should be considered, particularly in juvenile and young adult patients, to exclude differential diagnoses and to enable patients access to new treatment approaches., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Motor neuron disease (MND) is largely understudied in many underdeveloped and developing countries, including the Philippines. The practice and management of MND is generally insufficient, and thus, the quality of life of these patients are consequently compromised., Objectives: The aim of this study is to determine the clinical profile and describe the management of MND patients seen in the largest tertiary hospital in the Philippines for one year., Methods: This is a cross-sectional study of MND patients diagnosed clinically and via electromyogram-nerve conduction study (EMG NCS) in the Philippine General Hospital (PGH) from January to December 2022. Clinical characteristics, diagnostics and management information were obtained and summarized., Results: The incidence of MND in our neurophysiology unit was 4.3% (28/648), with amyotrophic lateral sclerosis (ALS) being the most common variant (67.9%, n = 19). Male to Female ratio was 1:1, with the median age of onset of 55 (36-72) years old and median onset duration to diagnosis of 1.5 (0.25-8) years. Limb onset was more prevalent (82.14%, n = 23) with upper limbs initially involved (79.1%, n = 18). Split hand syndrome was found in almost half (53.6%) of the patients. The median ALS functional rating score-revised (ALSFRS-R) and medical research council (MRC) scores were 34 (8-47) and 42(16-60) respectively while the median King's clinical stage was 3 (1-4). Only half of the patients were able to undergo magnetic resonance imaging (MRI) and only one had neuromuscular ultrasound. Only one of the 28 patients was able to take riluzole, and only one was on oxygen support. None had gastrostomy and none used non-invasive ventilation., Conclusion: This study showed that the management of MND in the Philippines is largely inadequate and further improvement in the health care system in handling rare neurologic cases must be implemented to enhance their quality of life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding: None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In the past, the diagnosis of motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and 5q-associated spinal muscular atrophy (SMA) meant powerlessness in the face of seemingly untreatable diseases with severe motor-functional limitations and sometimes fatal courses. Recent advances in an understanding of the genetic causalities of these diseases, combined with success in the development of targeted gene therapy strategies, spell hope for effective, innovative therapeutic approaches, pioneering the ability to treat neurodegenerative diseases. While gene therapies have been approved for SMA since a few years, gene therapy research in ALS is still in clinical trials with encouraging results. This article provides an overview of the genetic background of ALS and SMA known to date and gene therapy approaches to them with a focus on therapy candidates that are in clinical trials or have already gained market approval., Competing Interests: Teilnahme an advisory boards initiiert von Biogen, Roche, Zambon, ITF Pharma. Beratertätigkeit und Vorträge im Auftrag von Biogen. Forschungsunterstützung durch Biogen., (Thieme. All rights reserved.)

Introduction: Home mechanical ventilation can be used to manage symptoms of breathlessness and sustain life for people living with motor neuron disease (plwMND). In the UK, less than 1% of plwMND use tracheostomy ventilation (TV). This contrasts with some other countries, where rates are much higher. Due to a lack of evidence about its feasibility, cost-effectiveness or outcomes, TV is not covered in the UK National Institute for Health and Care Excellence guidance. Most plwMND receiving TV in the UK do so as an unplanned crisis intervention, which can lead to a prolonged hospital stay while a complex care package is arranged. There is insufficient literature addressing the burdens and benefits of TV, how it should be initiated and delivered, and how future care choices for plwMND can be supported. The aim of this research is to provide new understandings of the experiences of plwMND using TV, and those of family members and healthcare professionals (HCPs) involved in their care., Methods and Analysis: A UK-wide qualitative study with two workstreams: (1) Patient focused case studies (n=6) including plwMND, family members and HCPs to focus on experiences and tasks of daily living from multiple perspectives. (2) Interviews with plwMND (n=10), family members, including bereaved family members (n=10) and HCPs (n=20) on broader experiences and issues relating to use of TV, such as ethical considerations and decision making., Ethics and Dissemination: Ethical approval has been granted by the Leicester South Research Ethics Committee (22/EM/0256). All participants will be asked to provide electronic, written and/or audio recorded informed consent. Study findings will be disseminated in peer-reviewed journals and conference presentations and used to develop new resources for teaching and public information., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), causes increasing physical impairment and disability. People with ALS/MND face huge physical challenges, and the diagnosis can be a source of great psychological distress for both people with ALS/MND and their carers. In such a context, how news of the diagnosis is broken is important. At present, there are no systematic reviews of methods for informing people with ALS/MND of their diagnosis., Objectives: To examine the effects and effectiveness of different methods for informing people of a diagnosis of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), including effects on the person's knowledge and understanding of their disease, its treatment, and care; and on coping and adjustment to the effects of ALS/MND, its treatment, and care., Search Methods: We searched the Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and two trials registers (February 2022). We contacted individuals or organisations to locate studies. We contacted study authors to obtain additional unpublished data., Selection Criteria: We planned to include randomised controlled trials (RCTs) and quasi-RCTs of techniques for informing people with ALS/MND of their diagnosis. We planned to include adults (aged 17 years or over) with ALS/MND, according to the El Escorial criteria., Data Collection and Analysis: Three review authors independently reviewed the results of the search to identify RCTs, and three review authors identified non-randomised studies to include in the discussion section. We planned that two review authors would independently extract data, and three would assess the risk of bias in any included trials., Main Results: We did not identify any RCTs that met our inclusion criteria., Authors' Conclusions: There are no RCTs that evaluate different communication strategies for breaking the bad news for people diagnosed with ALS/MND. Focused research studies are needed to assess the effectiveness and efficacy of different communication methods., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that leads to the neurodegeneration and death of upper and lower motor neurons (MNs). Although MNs are the main cells involved in the process of neurodegeneration, a growing body of evidence points toward other cell types as concurrent to disease initiation and propagation. Given the current absence of effective therapies, the quest for other therapeutic targets remains open and still challenges the scientific community. Both neuronal and extra-neuronal mechanisms of cellular stress and damage have been studied and have posed the basis for the development of novel therapies that have been investigated on both animal models and humans. In this chapter, a thorough review of the main mechanisms of cellular damage and the respective therapeutic attempts targeting them is reported. The main areas covered include neuroinflammation, protein aggregation, RNA metabolism, and oxidative stress., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Clinicians report that withdrawal of mechanical ventilation in motor neuron disease is challenging. We report on the evaluation of the process and outcomes called for by the Association for Palliative Medicine of Great Britain and Ireland (APM) guidance., Methods: Excel analysis of a core data set, defined in the APM guidance, and thematic analysis of free-text comments, submitted by a UK clinician soon after withdrawal of mechanical ventilation in any care setting., Results: Thirty-seven professionals submitted 46 data sets from 4 patients with tracheostomy ventilation (TV) and 42 with non-invasive ventilation (NIV) in 35 months. These took place at home (43%), inpatient hospice (48%), hospital and care homes. Eighty-nine per cent received opioid and/or sedative medication at the initiation of withdrawal, majority of which were subcutaneous. A median of 2 doses (range 1-9) were used to manage symptoms before ventilation withdrawal. Subsequently 73% of patients required either none or one dose of medication. In addition to any background opioid, symptom management required a total parenteral morphine equivalent mean of 20.6 mg (range 0-60 mg) and midazolam mean of 25.8 mg (range 0-120 mg). The median time from first medication to removal of mechanical ventilation was 45 min. Patients with TV died within 30 min of withdrawal. The mode (14 of 42 patients) time to death after NIV withdrawal was 15 min, but ranged between <15 min and 54 hours., Conclusions: Individualised, proportionate, titrated opioid and sedative medications were used to provide good symptom management, and provided new insight into the substantial variability in what patients require to manage their symptoms and how long the process takes. Most patients required lower doses than in previous literature., Competing Interests: Competing interests: CF has received other competitive grant funding from the Motor Neurone Disease Association., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Motor neuron disease (MND) is a rapidly progressive, fatal neurodegenerative disease that predominantly affects motor neurons from the motor cortex to the spinal cord and causes progressive wasting and weakening of bulbar, limb, abdominal and thoracic muscles. Prognosis is poor and median survival is 2-3 years following symptom onset. Psychological distress is relatively common in people living with MND. However, formal psychotherapy is not routinely part of standard care within MND Care Centres/clinics in the UK, and clear evidence-based guidance on improving the psychological health of people living with MND is lacking. Previous research suggests that Acceptance and Commitment Therapy (ACT) may be particularly suitable for people living with MND and may help improve their psychological health., Aims: To assess the clinical and cost-effectiveness of ACT modified for MND plus usual multidisciplinary care (UC) in comparison to UC alone for improving psychological health in people living with MND., Methods: The COMMEND trial is a multi-centre, assessor-blind, parallel, two-arm RCT with a 10-month internal pilot phase. 188 individuals aged ≥ 18 years with a diagnosis of definite, laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis, and additionally the progressive muscular atrophy and primary lateral sclerosis variants, will be recruited from approximately 14 UK-based MND Care Centres/clinics and via self-referral. Participants will be randomly allocated to receive up to eight 1:1 sessions of ACT plus UC or UC alone by an online randomisation system. Participants will complete outcome measures at baseline and at 6- and 9-months post-randomisation. The primary outcome will be quality of life at six months. Secondary outcomes will include depression, anxiety, psychological flexibility, health-related quality of life, adverse events, ALS functioning, survival at nine months, satisfaction with therapy, resource use and quality-adjusted life years. Primary analyses will be by intention to treat and data will be analysed using multi-level modelling., Discussion: This trial will provide definitive evidence on the clinical and cost-effectiveness of ACT plus UC in comparison to UC alone for improving psychological health in people living with MND., Trial Registration: ISRCTN Registry, ISRCTN12655391. Registered 17 July 2017, https://www.isrctn.com/ISRCTN12655391 ., Protocol Version: 3.1 (10/06/2020)., (© 2022. The Author(s).)

Introduction: To capture the patient's attitude toward remote monitoring of motor neuron disease (MND) in care and clinical trials, and their concerns and preferences regarding the use of digital technology., Methods: We performed an international multi-centre survey study in three MND clinics in The Netherlands, the United Kingdom, and Australia. The survey was co-developed by investigators and patients with MND, and sent to patients by e-mail or postal-mail. The main topics included: patients' attitude towards remote care, participating in decentralized clinical trials, and preferences for and concerns with digital technology use., Results: In total, 332 patients with MND participated. A majority of patients indicated they would be happy to self-monitor their health from home (69%), be remotely monitored by a multidisciplinary care team (75%), and would be willing to participate in clinical trials from home (65%). Patients considered respiratory function and muscle strength most valuable for home-monitoring. The majority of patients considered the use of at least three devices/apps (75%) once a week (61%) to be acceptable for home-monitoring. Fifteen percent of patients indicated they would not wish to perform home-measurements; reporting concerns about the burden and distress of home-monitoring, privacy and data security., Conclusion: Most patients with MND exhibited a positive attitude toward the use of digital technology in both care and clinical trial settings. A subgroup of patients reported concerns with home-monitoring, which should be addressed in order to improve widespread adoption of remote digital technology in clinical MND care., (© 2022. The Author(s).)

Background: Communication and cognitive impairments are known barriers to shared decision-making. Most people diagnosed with motor neurone disease (MND) will develop a motor speech impairment over the disease course. Some will develop cognitive, linguistic or behavioural disturbance. Despite this, the impact of communication and cognitive impairment on personal healthcare decision-making in MND is not well known., Aims: This exploratory, longitudinal study aimed to capture the perspectives of people living with MND (plwMND) and family members on managing their healthcare with, or in anticipation of, a communication impairment., Methods & Procedures: Semi-structured interviews and functional assessments were conducted with plwMND and family members over one to three time points between December 2017 and January 2020. Participants were recruited from a specialist MND clinic using a maximum variation sampling approach. Interview transcripts were analysed using trajectory data analysis: a matrix-based approach for thematic analysis of longitudinal data. The study was underpinned by interpretive descriptive methodology., Outcomes & Results: A total of 19 plwMND with a range of MND phenotypes and 15 family members were recruited. Disease progression and participant withdrawal resulted in attrition, however 12 plwMND and seven family members participated at all three time points. Consistent cognitive screening was not feasible, which limited the opportunity to explore the impact of cognitive change. An overarching theme 'Communicating takes effort' was identified and illustrates the efforts required to compensate for, or circumnavigate, impairments to maintain involvement in healthcare. Assistance from family and accommodation from healthcare professionals (HCPs) was needed for ongoing engagement. Where plwMND were dependent on alternative communication devices, this assistance was essential and primarily carried out by family members. Despite these efforts, the quality, quantity and accuracy of communication were sometimes compromised. Participants equated good communication with receiving good healthcare, and some expressed anxiety in the anticipation of being unable to express their needs to healthcare workers., Conclusion & Implications: Communication impairment has a direct impact on healthcare involvement. This study demonstrates the effort required by plwMND and their carers to maintain or maximize ongoing involvement. This effort may not always be visible to HCPs. This information may prompt clinicians to consider the best ways to conduct clinical consultations to accommodate patients' abilities. Compromised communication experiences can be moderated by accommodations and support from HCPs and appropriate adjustments in the health system. Asking patients about their communication preferences and needs, allowing extra time and conducting multidisciplinary sessions are examples of such support., What This Paper Adds: What is already known on this subject? Communication and cognitive impairments are known contributors to negative health outcomes and barriers to shared decision-making generally. The existing literature in decision-making in MND does not address the specific impact of these impairments on personal healthcare involvement for plwMND and their carers. What this paper adds to existing knowledge? This paper reports the findings of a research project that interviewed 19 plwMND and 15 carers on one to three occasions over a 26-month period to obtain their perspectives of the impact of communication on healthcare involvement. Whilst a priori the intention was to look at both communicative and cognitive decline, only the former was achieved. The effort and often 'invisible' activity undertaken to manage or maintain involvement in healthcare is identified. Communication impairment requires support and accommodation, otherwise healthcare involvement can be compromised. Results show participants may associate effective communication with good healthcare. What are the potential or actual clinical implications of the work? Clinicians may wish to use these insights from plwMND and their carers to guide adjustments to their professional practice to maximize healthcare involvement for their patients. Tailored education for different healthcare groups is needed to improve understanding of MND-related communication impairments and supportive strategies so that involvement in healthcare is not compromised., (© 2022 The Authors. International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.)

Promising treatments for upper motor neuron disease are emerging in which motor function is restored by brain-computer interfaces and functional electrical stimulation. At present, such technologies and procedures are not applicable to lower motor neuron disease. We propose a novel therapeutic strategy for lower motor neuron disease and injury integrating neural stem cell transplantation with our new functional electrical stimulation control system. In a rat sciatic nerve transection model, we transplanted embryonic spinal neural stem cells into the distal stump of the peripheral nerve to reinnervate denervated muscle, and subsequently demonstrated that highly responsive limb movement similar to that of a healthy limb could be attained with a wirelessly powered two-channel neurostimulator that we developed. This unique technology, which can reinnervate and precisely move previously denervated muscles that were unresponsive to electrical stimulation, contributes to improving the condition of patients suffering from intractable diseases of paralysis and traumatic injury.

An innovative approach to patient management, evidence-based policy development, and clinical drug trials is required to provide personalized care and to improve the likelihood of finding an effective treatment for Motor Neurone Disease (MND). The MiNDAus Partnership builds on and extends existing national collaborations in a targeted approach to improve the standard and coordination of care for people living with MND in Australia, and to enhance the prospects of discovering a cure or treatment. Relationships have been developed between leading clinical and research groups as well as patient-centered organizations, care providers, and philanthropy with a shared vision. MiNDAus has established a corporate structure and meets at least biannually to decide on how best to progress research, drug development, and patient management. The key themes are; (i) empowering patients and their family carers to engage in self-management and ensure personalized service provision, treatment, and policy development, (ii) integration of data collection so as to better inform policy development, (iii) unifying patients and carers with advocacy groups, funding bodies, clinicians and academic institutions so as to inform policy development and research, (iv) coordination of research efforts and development of standardized national infrastructure for conducting innovative clinical MND trials that can be harmonized within Australia and with international trials consortia. Such a collaborative approach is required across stakeholders in order to develop innovative management guidelines, underpinned by necessary and evidence-based policy change recommendations, which, will ensure the best patient care until a cure is discovered.

Gene therapy is a revolutionary, cutting-edge approach to permanently ameliorate or amend many neuromuscular diseases by targeting their genetic origins. Motor neuron diseases and muscular dystrophies, whose genetic causes are well known, are the frontiers of this research revolution. Several genetic treatments, with diverse mechanisms of action and delivery methods, have been approved during the past decade and have demonstrated remarkable results. However, despite the high number of genetic treatments studied preclinically, those that have been advanced to clinical trials are significantly fewer. The most clinically advanced treatments include adeno-associated virus gene replacement therapy, antisense oligonucleotides, and RNA interference. This review provides a comprehensive overview of the advanced gene therapies for motor neuron diseases (i.e., amyotrophic lateral sclerosis and spinal muscular atrophy) and muscular dystrophies (i.e., Duchenne muscular dystrophy, limb-girdle muscular dystrophy, and myotonic dystrophy) tested in clinical trials. Emphasis has been placed on those methods that are a few steps away from their authoritative approval.

In many international care guidelines, multidisciplinary palliative care forms a key to optimum management in Motor Neuron Disease (MND). We describe the home-based palliative care interventions for a client with MND and his family from a Low and Middle-income country context. This report also discusses the advantages and challenges of the same with suggestions for sustaining the quality of care for neuro palliative conditions.

Despite recent and potent technological advances, the real-world implementation of remote digital health technology in the care and monitoring of patients with motor neuron disease has not yet been realized. Digital health technology may increase the accessibility to and personalization of care, whereas remote biosensors could optimize the collection of vital clinical parameters, irrespective of patients' ability to visit the clinic. To facilitate the wide-scale adoption of digital health care technology and to align current initiatives, we outline a road map that will identify clinically relevant digital parameters; mediate the development of benefit-to-burden criteria for innovative technology; and direct the validation, harmonization, and adoption of digital health care technology in real-world settings. We define two key end products of the road map: (1) a set of reliable digital parameters to capture data collected under free-living conditions that reflect patient-centric measures and facilitate clinical decision making and (2) an integrated, open-source system that provides personalized feedback to patients, health care providers, clinical researchers, and caregivers and is linked to a flexible and adaptable platform that integrates patient data in real time. Given the ever-changing care needs of patients and the relentless progression rate of motor neuron disease, the adoption of digital health care technology will significantly benefit the delivery of care and accelerate the development of effective treatments., (©Ruben P A van Eijk, Anita Beelen, Esther T Kruitwagen, Deirdre Murray, Ratko Radakovic, Esther Hobson, Liam Knox, Jochem Helleman, Tom Burke, Miguel Ángel Rubio Pérez, Evy Reviers, Angela Genge, Frederik J Steyn, Shyuan Ngo, John Eaglesham, Kit C B Roes, Leonard H van den Berg, Orla Hardiman, Christopher J McDermott. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.09.2021.)

Objectives: Motor neuron disease (MND) is a neurodegenerative disorder leading to functional decline and death. Multidisciplinary MND clinics provide an integrated approach to management and facilitate discussion on advanced care directives (ACDs). The study objectives are to analyse (1) the prevalence of ACD in our MND clinic, (2) the relationship between ACD and patient demographics and (3) the relationship between ACD decision-making and variables such as NIV, PEG, hospital admissions and location of death., Methods: Using clinic records, all patients who attended the MND clinic in Liverpool Hospital between November 2014 and November 2019 were analysed. Data include MND subtypes, symptom onset to time of diagnosis, time of diagnosis to death, location and reason of death. ACD prevalence, non-invasive ventilation (NIV) and percutaneous endoscopic gastrostomy (PEG) requirements were analysed., Results: There were 78 patients; M:F=1:1. 44 (56%) patients were limb onset, 28 (36%) bulbar onset, 4 primary lateral sclerosis and 2 flail limb syndrome presentations. 27% patients completed ACDs, while 32% patients declined ACDs. Patients born in Australia or in a majority English-speaking country were more likely to complete ACDs compared to those born in a non-English-speaking country. There was no significant correlation between ACD completion and age, gender, MND subtype, symptom duration, NIV, PEG feeding, location of death., Conclusion: One-quarter of patients completed ACDs. ACDs did not correlate with patient age, gender, MND subtype and symptom duration or decision-making regarding NIV, PEG feeding or location of death. Further studies are needed to address factors influencing patients' decisions regarding ACDs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)