Amyotrophic lateral sclerosis (ALS) is a life-threatening disease characterised by progressive loss of motor neurons with few therapeutic options. The MIROCALS study tested the hypothesis that low-dose interleukin-2 (IL-2LD) improves survival and function in ALS. In this randomised, double-blind, placebo-controlled trial, male and female riluzole-naive participants, with either a possible, laboratory-supported probable, probable, or definite ALS diagnosis (revised El Escorial criteria), aged 18-76 years, with symptom duration of 24 months or fewer, and slow vital capacity of 70% or more, underwent a riluzole-only 12-18 week run-in period before randomisation in a 1:1 ratio to either 2 million international units (MIU) IL-2LD or placebo by subcutaneous injection daily for 5 days every 28 days over 18 months. The primary endpoint was survival at 640 days (21 months). Secondary outcomes included safety, ALS Functional Rating Scale-Revised (ALSFRS-R) score, and biomarker measurements including regulatory T-cells (Tregs), cerebrospinal fluid (CSF)-phosphorylated-neurofilament heavy-chain (CSF-pNFH), and plasma and CSF-chemokine ligand 2 (CCL2). The primary endpoint analysis used unadjusted log-rank and Cox's model adjusted analyses using pre-defined prognostic covariates to control for the disease and treatment response heterogeneity. The study was 80% powered to detect a two-fold decrease in the risk of death by the log-rank test in the intention-to-treat (ITT) population, including all randomly allocated participants. MIROCALS is registered with ClinicalTrials.gov (NCT03039673) and is complete. From June 19, 2017, to Oct 16, 2019, 304 participants were screened, of whom 220 (72%) met all criteria for random allocation after the 12-to-18-week run-in period on riluzole. 136 (62%) of participants were male and 84 participants (38%) were female. 25 (11%) of the 220 randomly allocated participants were defined as having possible ALS under El Escorial criteria. At the cutoff date there was no loss to follow-up, and all 220 patients who were randomly allocated were documented as either deceased (90 [41%]) or alive (130 [59%]), so all participants were included in the ITT and safety populations. The primary endpoint unadjusted analysis showed a non-significant 19% decrease in risk of death with IL-2LD (hazard ratio 0·81 [95% CI 0·54-1·22], p=0·33), failing to demonstrate the expected two-fold decrease in risk of death. The analysis of the primary endpoint adjusted on prognostic covariates, all measured at time of random allocation, showed a significant decrease of the risk of death with IL-2LD (0·32 [0·14-0·73], p=0·007), with a significant treatment by CSF-pNFH interaction (1·0003 [1·0001-1·0005], p=0·001). IL-2LD was safe, and significantly increased Tregs and decreased plasma-CCL2 at all timepoints. Stratification on CSF-pNFH levels measured at random allocation showed that IL-2LD was associated with a significant 48% decrease in risk of death (0·52 [0·30-0·89], p=0·016) in the 70% of the population with low (750-3700 pg/mL) CSF-pNFH levels, while in the 21% with high levels (>3700 pg/mL), there was no significant difference (1·37 [0·68-2·75], p=0·38). With this treatment schedule, IL-2LD resulted in a non-significant reduction in mortality in the primary unadjusted analysis. However, the difference between the results of unadjusted and adjusted analyses of the primary endpoint emphasises the importance of controlling for disease heterogeneity in ALS randomised controlled trials. The decrease in risk of death achieved by IL-2LD therapy in the trial population with low CSF-pNFH levels requires further investigation of the potential benefit of this therapy in ALS. European Commission H2020 Programme; French Health Ministry PHRC2014; and Motor Neurone Disease Association.

Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK

BackgroundMotor Neurone Disease (MND), is a debilitating neurodegenerative condition, which significantly impacts the quality of life of those affected. Neck weakness is one challenge faced by those living with MND and as such may require a neck collar to assist. However, the user experience and requirements related to these neck collars have not been comprehensively explored. Understanding these priorities is crucial for enhancing the well-being of MND patients. ObjectiveTo understand the priorities of people living with Motor Neurone Disease (MND) including user experience, requirements and the importance of neck collars used to aid neck weakness. MethodsAn online survey was used to investigate the perspectives and experiences of off the shelf neck collars used by people living with MND. The MND Association was selected as a strategic partner by their affiliations and access to large data base of MND patients. ResultsSurvey highlighted a disparity between the actual duration MND patients wear their current neck collars and their desired duration, emphasising the need to integrate collars into daily activities. Key areas for improvement with existing neck collars centred on comfort and reduced restriction, with respondents expressing a preference for collars that offer support without impeding movement. Additionally, addressing pressure on the anterior neck region during collar use emerged as a critical requirement. ConclusionCurrent collars do not cause any clinical complications; however, they do fall short of meeting the expected needs of people living with MND, including discomfort, restricted movement, and pressure to the anterior region of the neck. This study highlights need to improve current collar designs to provide better quality of life for MND patients.

Background:Family caregivers of people with motor neurone disease (MND) experience adverse health outcomes as a result of their caregiving experience. This may be alleviated if their support needs are identified and addressed in a systematic and timely manner. The objective of this pilot study was to assess the feasibility and relevance of the Carers’ Alert Thermometer (CAT) in home-based care, from the perspective of MND family caregivers. The tool provides a formal structure to facilitate discussions with caregivers to enable needs to be addressed.Methods:This mixed-method study was conducted in Western Australia (2020–2021). Forty-one caregivers and five MND Advisors participated in trialling the CAT intervention which consisted of two encounters with Advisors (6–8 weeks apart) to identify and address support needs through action plans. Caregivers’ feedback was obtained via telephone interviews and a thematic analysis was undertaken.Results:Thirty caregivers completed two CAT assessments. Caregivers identified support priorities of managing their feelings and worries, providing emotional or spiritual care, information about the person’s condition and how their care needs might change. Seventeen caregivers were interviewed and found that this assessment process adequately addressed their needs and it should be continued, it brought the focus onto them to clarify problems and work through solutions. The improvements that were suggested by them, including better information/education in palliative care, led to the development of an online support/information toolkit, which served to empower caregivers and staff by accessing relevant information and resources.Conclusions:The CAT demonstrated utility for triaging caregivers most in need of additional support and those whom signposting to additional information and self-directed access to support was most appropriate. For any tool to become an integrated part of care, service provider support is key for implementation, allowing for the time resource required and an appropriate education and support structure. MND Associations have an important role in building stronger partnerships with supportive community networks, through compassionate communities models of care, to address the identified needs of MND families in a more sustainable and wholistic manner. Needs assessment is a means towards building this capacity between formal and informal networks.

Introduction: Motor neurone disease is a life limiting progressive neurological condition that requires a team-based approach to care. Person-centred care (PCC), integrated care and access to specialised motor neurone disease (MND) multidisciplinary clinics (MDC) are optimal approaches to the delivery of quality service for people living with MND (plwMND) for improved quality of life, health outcomes and care experiences. These MND MDCs models of care vary in design, implementation, and are predominantly specialist hospital based. Therefore, not all MND services are delivered consistently highlighting a need to explore the evidence on current practices that contribute to more effective, efficient person-centred integrated care practices across the continuum. Aim: This rapid review explores best practices of integrated care for people living with motor neurone disease, and their families and carers. Methods: A search was undertaken of six databases, Medline (Ovid), Embase (Ovid), CINAHL, Cochrane, Joanna Briggs Institute and Google Scholar. The 1469 retrieved abstracts were screened for eligibility against the inclusion criteria, and full text review was conducted on 149 studies. Data were extracted from 58 studies and a quality assessment conducted on final 45 included studies. The following information was gathered from the included studies to inform the review. 1.What is ‘best practice’ in the management/care of plwMND 2.What models of (integrated) care have been developed to support plwMND 3.What are the common elements of integrated care approaches that have been implemented in MND? 4.What impacts, outcomes, or effects of integrated care approaches have been reported for plwMND? Results: The initial review analysis indicated specialised MND multidisciplinary clinics (MDC) as ‘best practice’ in the optimal management of MND, but revealed no standardised approaches in design and implementation, the multidisciplinary workforce, and degree of integration and partnerships between hospitals and the community. MND MDC are predominantly hospital based, but the inclusion of either outreach community teams, hub and spoke approaches, and/or a hybrid design, (care delivered in person and /or by telehealth), improved integration, knowledge sharing and coordination across services. The timing of introduction and delivery of palliative care services differs but there is greater focus on integration into MND MDC, or earlier referrals to dedicated palliative care service and/or specific palliative care training of neurologist/multidisciplinary team, to optimise symptom management, decision-making and end of life care. Additional features that enable integration, improve care satisfaction and equity are one or a mix of 1) telehealth, 2) care coordination, 3) case management, 4) partnerships with MND associations, and/or 5) MND helpline. Conclusion: This review highlights a range of practices of integrated care that are not universal and predominantly practiced in high income countries. Adapting delivery of model of care to stage and duration of MND, and differing expectations, needs and priorities of plwMND and caregivers, is a common theme throughout. There has been greater uptake in telehealth and technology to support the equitable delivery of integrated approaches to care, with rapid development in this area during COVID 19 pandemic.

It is estimated that up to ten per cent of people with motor neurone disease (MND) have an inherited form of the disease. Families with a history of inherited MND may face specific issues around managing the condition in relatives and adapting to life knowing that they too could develop the disease, which we refer to as living ‘at risk’. This qualitative study is based on a thematic analysis of posts from 37 threads shared on the MND Association Forum between 2010 and 2019. Through this analysis we explore how forum users make sense of, and negotiate, genetic risk in this online space. We unpack how risk is constructed through a tracing and reframing of family history in relation to MND; we draw out the different ways uncertainty is expressed by people living with the threat of the disease; and we outline how future decisions around genetic testing and reproductive choices play out on the forum. Genetic risk was articulated temporally, with posters reflecting on past, present and expected future experiences across posts. This was crosscut by profound uncertainty. How people understood and expressed experiences of living ‘at risk’ – and the responses they received from others – were grounded in different forms of experiential knowledge, intertwined with biomedical and genetic information. We propose the MND Association forum as an interactional site where uncertainties are negotiated and risk is made sense of by individuals with a family history of MND, alongside those affected by ‘sporadic’ forms of the disease.

Background:Studies on the experiences of consumers with Motor Neurone Disease Associations at end of life and bereavement are lacking, and their role and capability within the broader sectors of health and disability are unknown.Objectives:To ascertain the experiences and views of bereaved motor neurone disease caregivers with Motor Neurone Disease Associations about service gaps and needed improvements before and during bereavement and to propose a model of care that fits with consumer preferences and where Motor Neurone Disease Associations are effective enablers of care.Methods:A national bereavement survey was facilitated in 2019 by all Motor Neurone Disease Associations in Australia. A total of 363 respondents completed the section on support provided by Motor Neurone Disease Associations. A mixed-method design was used.Results:Respondents were generally positive about support received before bereavement (73-76%), except for emotional support (55%). Positive experiences related to the following: information, equipment advice/provision, advocacy/linking to services, showing empathy/understanding, personal contact and peer social support. Negative experiences included lack of continuity in case management and contact, perceived lack of competence or training, lack of emotional support and a lack of access to motor neurone disease services in rural areas. Suggested improvements were as follows: more contact and compassion at end of life and postdeath; better preparation for end of life; option of discussing euthanasia; providing referrals and links for counseling; access to caregiver support groups and peer interaction; provision of a genuine continuum of care rather than postdeath abandonment; guidance regarding postdeath practicalities; and more access to bereavement support in rural areas.Conclusion:This study provides consumer perspectives on driving new or improved initiatives by Motor Neurone Disease Associations and the need for a national standardised approach to training and service delivery, based on research evidence. A public health approach to motor neurone disease end-of-life care, of international applicability, is proposed to address the needs and preferences of motor neurone disease consumers, while supporting the capability of Motor Neurone Disease Associations within a multidisciplinary workforce to deliver that care.

Background:There are few illnesses as disruptive as motor neurone disease, a fatalneurodegenerative condition, where diagnosis introduces a clinical narrativeof inevitable decline through progressive immobilisation into death. Recentevidence suggests that bereaved motor neurone disease family caregivers aremore likely to be at moderate or high risk of complicated grief.Methods:Qualitative data from an anonymous national survey of bereaved motor neuronedisease caregivers (n = 393) was examined through thematicanalysis to explore the experiences of people who are at low, moderate, andhigh risk of complicated grief. Up to 40% responded to three open-endedquestions: How caregivers viewed their coping strategies; the advice theyhad for others and what had been positive about their experience.Results:Ten themes informed the narratives of illness and loss. All three groupsshared similar experiences but differed in their capacity to address them.The low-risk group seemed to recognise the uncertainty of life and thatmeaning needed to be created by them. For the moderate-risk group, whilemotor neurone disease was a major disruption, they could with support,regroup and plan in different ways. The high-risk group did not have manyresources, external or internal. They felt let down when professionals didnot have answers and could not see or did not know how to change their waysof responding to this unwanted situation.Conclusion:The differences in these three profiles and their narratives of loss shouldalert health and community service providers to identify and address thecaregivers’ support needs early and throughout the caregiving journey. MotorNeurone Disease Associations are involved throughout the illness journey andneed to invest in a continuum of care incorporating end-of-life care andbereavement support. Community grief literacy and enhancement of socialnetworks are keys to improved support from families and friends that canenable the focus to be on feelings of empowerment rather thanabandonment.

Background Although Motor Neurone Disease (MND) caregivers are most challenged physically and psychologically, there is a paucity of population-based research to investigate the impact of bereavement, unmet needs, range of supports, and their helpfulness as perceived by bereaved MND caregivers. Methods: An anonymous national population-based cross-sectional postal and online survey of bereavement experiences of family caregivers who lost a relative/friend to MND in 2016, 2017, and 2018. Recruitment was through all MND Associations in Australia. Results: 393 valid responses were received (31% response rate). Bereaved caregiver deterioration in physical (31%) and mental health (42%) were common. Approximately 40% did not feel their support needs were met. Perceived insufficiency of support was higher for caregivers at high bereavement risk (63%) and was associated with a significant worsening of their mental and physical health. The majority accessed support from family and friends followed by MND Associations, GPs, and funeral providers. Informal supports were reported to be the most helpful. Sources of professional help were the least used and they were perceived to be the least helpful. Conclusions: This study highlights the need for a new and enhanced approach to MND bereavement care involving a caregiver risk and needs assessment as a basis for a tailored “goodness of fit” support plan. This approach requires continuity of care, more resources, formal plans, and enhanced training for professionals, as well as optimizing community capacity. MND Associations are well-positioned to support affected families before and after bereavement but may require additional training and resources to fulfill this role.

Background Despite the traumatic and fatal nature of motor neurone disease (MND) and the caring experiences being described as unrelenting, little is known about risk of psychiatric morbidity and Prolonged Grief Disorder (PGD) for family caregivers. Methods: A cross-sectional survey of caregivers bereaved in 2016-2018 was distributed by the five MND Associations in Australia (2019). Validated tools for PGD (PG-13), anxiety, depression, and family functioning were included. Multinomial logistic regression was used to compare the factors associated with grief. Findings: Overall, 393 valid responses were received, a 31% response rate. The prevalence of ICD-11 PGD was 9.7%; moderate/severe anxiety 12.3%, moderate/severe depression 18.5% and 18.7% indicated poor family functioning. MND caregivers have higher bereavement risk prevalence than the general bereaved population, with 9.6% in the high-risk group (vs 6.4%) and 54% at moderate risk (vs 35%). Being in the PGD group was 8 or 18 times more likely when the respondent had anxiety or depression, respectively. Poor family functioning significantly increased the likelihood of PGD by four times. Other significant predictors of PGD were a recent bereavement (<12 months), being a spouse/partner of the deceased, insufficient support during the disease journey, the deceased being under 60 years of age, and a shorter period of caring (<1.5 years). Conclusion: In a large national population-based sample of bereaved MND caregivers, 63% required bereavement support over and above that provided by family and social networks. This is a neglected yet seriously ill population that calls for better care provision and clinical practice.

Background: Burden and distress among family carers of people living with motor neurone disease (MND) are reported widely. Evidence-based screening tools to help identify these carers' needs and plan appropriate support are urgently needed. Aim: To pilot the Carers' Alert Thermometer (CAT), a triage tool developed to identify carers' needs, with family carers of people living with MND to determine its usefulness in identifying their need for support. Methods: Training workshops with MND Association visitors (AVs) and staff in southwest and northwest England, followed by implementation of the CAT. A self-completed online survey and semi-structured telephone interview evaluated use of the CAT. Findings: Sixteen participants completed the online survey with 11 volunteering to be interviewed. The CAT has potential to map change over time, help to focus on carers' needs and improve communication with carers. Conclusion: The CAT provides a structure enabling AVs to engage in a meaningful process with family carers to identify and discuss their needs.

ObjectivesTo assess associations between occupation and motor neuron disease (MND).MethodsWe conducted a population-based case–control study with cases (n=321) recruited through the New Zealand Motor Neurone Disease Association and hospital discharge...

ObjectiveThere is an immense socioeconomic burden for both the patients with motor neuron disease (MND) and their families. The aim of this study is to evaluate the extent to which...

… I would like to discuss my longevity as my fear of life is greater than death … quote from a person with MND. With no known cure and no effective treatment yet available for Motor Neurone Disease (MND), this article focusses on quality of life, quality of care and quality of death, the three outcomes of a palliative approach to caring for people with MND (PwMND) and their family carers. A palliative approach emphasizes the need for a patient and family-centred care that focuses on the person and not only on the illness, the importance of therapeutic interactions between care providers and the patient and family, a clear communication all through the illness trajectory and it stresses in particular, the importance of goals of care and advance care plans.A palliative approach needs to be integrated into the care plan for PwMND from the time of diagnosis, aiming to optimise their quality of life by relieving symptoms, providing emotional, psychological and spiritual support pre-bereavement, minimising barriers to a good death and supporting the family post-bereavement. However, these outcomes cannot be achieved without the following cornerstones of a palliative approach to MND care which starts with an empathetic delivery of the diagnosis, the vital support of family carers, the involvement of MND Associations, the education and training of general health and community care practitioners and the connection between the informal caring networks with the formal networks, as exemplified by Compassionate Communities policies and practices.The present article describes a number of evidence-based initiatives from diagnosis to bereavement that need to be implemented in standard practice in order to improve the health and social care of PwMND and their family carers. The drive to find a cure should not detract from the fact that PwMND and their families still need to be supported physically and psychologically until then, by all service providers using a palliative approach, through the continuum of care from start to end.

Initial Identification of a Blood-Based Chromosome Conformation Signature for Aiding in the Diagnosis of Amyotrophic Lateral Sclerosis

BackgroundThe availability of an increasing number of online health forums has altered the experience of living with a health condition, as more people are now able to connect and support one another. Empathy is an important component of peer-to-peer support, although little is known about how empathy develops and operates within online health forums.ObjectiveThe aim of this paper is to explore how empathy develops and operates within two online health forums for differing health conditions: breast cancer and motor neuron disease (MND), also known as amyotrophic lateral sclerosis.MethodsThis qualitative study analyzed data from two sources: interviews with forum users and downloaded forum posts. Data were collected from two online health forums provided by UK charities: Breast Cancer Care and the Motor Neurone Disease Association. We analyzed 84 threads from the breast cancer forum and 52 from the MND forum. Threads were purposively sampled to reflect varied experiences (eg, illness stages, topics of conversation, and user characteristics). Semistructured interviews were conducted with 14 Breast Cancer Care forum users and five users of the MND forum. All datasets were analyzed thematically using Braun and Clarke’s six-phase approach and combined to triangulate the analysis.ResultsWe found that empathy develops and operates through shared experiences and connections. The development of empathy begins outside the forum with experiences of illness onset and diagnosis, creating emotional and informational needs. Users came to the forum and found their experiences and needs were shared and understood by others, setting the empathetic tone and supportive ethos of the forum. The forum was viewed as both a useful and meaningful space in which they could share experiences, information, and emotions, and receive empathetic support within a supportive and warm atmosphere. Empathy operated through connections formed within this humane space based on similarity, relationships, and shared feelings. Users felt a need to connect to users who they felt were like themselves (eg, people sharing the same specific diagnosis). They formed relationships with other users. They connected based on the emotional understanding of ill health. Within these connections, empathic communication flourished.ConclusionsEmpathy develops and operates within shared experiences and connections, enabled by structural possibilities provided by the forums giving users the opportunity and means to interact within public, restricted, and more private spaces, as well as within groups and in one-to-one exchanges. The atmosphere and feeling of both sites and perceived audiences were important facilitators of empathy, with users sharing a perception of virtual communities of caring and supportive people. Our findings are of value to organizations hosting health forums and to health professionals signposting patients to additional sources of support.

‘The shock of diagnosis’: Qualitative accounts from people with Motor Neurone Disease reflecting the need for more person-centred care

While the experiences of family members supporting a person with a terminal illness are well documented, less is known about the needs of carers of people with neurological diseases, in particular, Motor Neurone Disease (MND). This paper describes the qualitative data from a large Australian survey of family carers of people with MND, to ascertain their experiences of receiving the diagnosis. The aim of the study was to describe the experiences of family carers of people with MND in receiving the diagnosis in order to inform and improve ways in which the diagnosis is communicated. Anonymous postal surveys were sent to people with MND in Australia and their family carers respectively. The perceived ability/skills of neurologists was assessed using a five-point scale from excellent to poor. Attributes of communication of bad news was measured by the SPIKES protocol. Each survey question invited further written responses. Eight hundred and sixty-four questionnaires were posted to people with MND and their family carers, with assistance from MND associations. One hundred and ninety-six family carers submitted responses, of which 171 (88%) were patient-carer dyads. Analyses were conducted on 190 family carers. Five themes emerged from reading and re-reading written responses: frustrations with the diagnosis; giving information; family carer observations of the neurologist; the setting; and what would have made the diagnosis easier? The delivery of the diagnosis is a pivotal event in the MND trajectory. Satisfaction for patients and their family carers is related to the neurologists showing empathy and responding appropriately to their emotions, exhibiting knowledge and providing longer consultations. Neurologists may benefit from education and training in communication skills to adequately respond to patients' and families' emotions and development of best practice protocols.

Background: Motor neurone disease (MND) is an incurable neurodegenerative condition. Recent guidelines from the MND Association UK (MNDA) emphasise prompt diagnosis and monitoring of quality of life (QOL). However, primary literature indicates that diagnosis is often delayed through several factors, including unawareness of how MND presents and delays through multiple secondary referrals. The [hospital] operates an internationally-recognised MND clinic whose service has not been audited against the MNDA UK guidelines for the last 3 years.Aim: To assess how well the MND consultant’s service ensures prompt diagnosis and the provision of end-of-life care or appropriate respiratory or nutritional support.Methods: Using the [hospital’s] database, records from 77 patients consulted consecutively in the MND clinic were obtained. Service parameters were compared against reference standards for diagnostic delay and treatment provision.Results: 84.4% of referrals came from neurologists outside of the MND service, with only 13% from general practitioners. On average, it took 14.7 months for patients to be seen in the MND clinic following symptom onset. Riluzole and percutaneous endoscopic gastrostomy (PEG) were prescribed faster in bulbar-onset versus limb-onset patients, by 4 times and 9 times respectively. End-of-life care discussion was recorded for 26% of patients.Conclusion: Diagnosing MND remains challenging for primary care physicians, which may be alleviated by disseminating recent Red Flag Committee guidelines. Investigation and treatment provision differed between MND subtypes, given the poorer prognosis associated with bulbar-onset. End-of-life care documentation remains low, which is an issue for the multi-disciplinary team (MDT) to resolve through incorporating palliative services.

Family carers of people with motor neurone disease (MND) face many difficulties before and after bereavement; their support needs are not routinely assessed and little attention is paid to recognising abnormal grief responses. The authors‘ survey (n=56) sought the views of those involved in the care of this population in England (Motor Neurone Disease Association regional care development advisers, staff working in motor neurone disease care and research centres and other health professionals) on bereavement support and prolonged grief disorder in family carers. Results revealed that more than two-thirds of respondents felt unable to predict future cases of prolonged grief disorder (PGD) and that an alert tool to help identify at-risk carers of people with MND would be welcomed. The implications for future research and development of support are also discussed within this article.