Measurement properties of the EQ-5D-Y-3L, PedsQL 4.0, and PROMIS-25 Profile v2.0 in pediatric patients with spinal muscular atrophy.

OBJECTIVE: The objective of this study was to examine the psychometric properties of the EQ-5D-Y-3 L, Patient Reported Outcomes Measurement System 25-item version profile v2.0 (PROMIS-25), and Pediatric Quality of Life Inventory™ version 4.0 Generic Core Scale (PedsQL 4.0) in Chinese pediatric patients with spinal muscular atrophy (SMA). METHODS: The data used in this study were obtained via a web-based cross-sectional survey. Parents of pediatric patients with SMA completed the proxy-reported EQ-5D-Y-3 L, PedsQL 4.0, and PROMIS-25 measures. Information about socioeconomic and health status was also obtained. The ceiling and floor effects, factorial structure, convergent validity, and known-group validity of the three measures were assessed. RESULTS: Three hundred and sixty-three parents of children aged from 5 to 12 completed the questionnaires. Strong floor effects were observed for the physical function components of the PROMIS-25 (41.3%) and PedsQL 4.0 (67.8%). For EQ-5D-Y-3 L, 84.6% of the respondents reported having "a lot of" problems with the dimensions "walking" and "looking after myself." Minimal ceiling or floor effects were observed for the EQ-5D-Y-3 L index value. The confirmatory factor analysis supported a six-factor structure for the PROMIS-25, but did not support a four-factor structure for the PedsQL 4.0. All hypothesized correlations of the dimensions among the three measures were confirmed, with coefficients ranging from 0.28 to 0.68. Analysis of variance showed that EQ-5D-Y-3 L demonstrated better known-group validity than the other two measures in 14 out of 16 comparisons. CONCLUSIONS: The EQ-5D-Y-3 L showed better discriminant power than the other two measures. The physical health dimensions of all three measures showed the significant floor effects. These findings provide valuable insights into the effectiveness of these measures at capturing and quantifying the impact of SMA on patients' health-related quality of life.

Health-related quality of life of adults with spinal muscular atrophy: insights from a nationwide patient registry in Germany.

PURPOSE: Spinal muscular atrophy (SMA) is a rare, autosomal-recessive disease characterized by progressive muscular atrophy and weakness resulting in substantial disability and short life expectancy. The objective of this cross-sectional study was to assess health-related quality of life (HRQoL) of adults with SMA in Germany in the era of disease-modifying therapy. METHODS: Adults with SMA were recruited via the German national TREAT-NMD SMA patient registry. HRQoL was measured using the EQ-5D-5L, the Health Utilities Index Mark III (HUI), and the Short Form (36) Health Survey (SF-36). Estimates were stratified by current best motor function of the lower limb and trunk (i.e., non-sitter, sitter, and walker) and SMA type (i.e., type I, II, and III). RESULTS: A total of 82 adults with SMA (mean age: 42 years, 51% female) self-completed the study questionnaire. The mean EQ-5D-5L utility was estimated at 0.5135 (range across subgroups: 0.31-0.99), mean EQ-VAS at 69.71 (64.67-90.00), mean HUI-derived utility at 0.3171 ( - 0.02-0.96), mean SF-6D utility at 0.6308 (0.58-0.65), and mean SF-36 Physical Component Summary and Mental Health Component Summary scores at 33.78 (9.92-53.10) and 53.49 (21.02-72.25), respectively. CONCLUSIONS: We show that adults with SMA experience considerable impairment across a wide range of health dimensions, including mobility, dexterity, pain, and emotional well-being. However, our results exhibit non-trivial variability across clinical subgroups and HRQoL measures. These data contribute to our understanding of the subjective impact of living with a severely debilitating neuromuscular disease, such as SMA.

Neurocognitive profile of a cohort of SMA type 1 pediatric patients and emotional aspects, resilience and coping strategies of their caregivers.

Spinal muscular atrophy (SMA) type 1 represents the most severe condition of the spectrum of SMA 5q. In the absence of therapeutic interventions, patients do not achieve any motor milestone and their life expectancy does not exceed two years of age. To date, three disease-modifying drugs have been approved for SMA type I. These treatments have radically changed the natural history of the disease, improving motor, respiratory and bulbar functions. In recent years huge amount of data have been collected worldwide related to motor, respiratory and swallowing function outcome in treated patients, whereas the neurocognitive profile of treated patients has been poorly explored. Here we report the neurocognitive development profile of a cohort of SMA type I children treated with a disease modifying therapy. We also describe the burden and resilience as well as the coping strategies of their caregivers. Our finding show a global developmental delay in most patients and defects in gross motor functions contribute most to lower the general development quotient of Griffiths III, whereas the scores obtained on evaluating learning and language abilities scales suggest a positive trend in the developmental trajectory of general neurocognitive abilities. Some parents reported anxiety and stress but overall they were resilient (and had good coping strategies towards the burden of care for their child. These results reinforce the importance of routinely assessing the neurocognitive aspects in SMA type I patients and to offer an early intervention to favor the psychosocial development of these children.

Current attitudes toward carrier screening for spinal muscular atrophy among pregnant women in Eastern China.

Spinal muscular atrophy (SMA) is an autosomal recessive and often fatal neurological disease. However, very little is known about the attitudes toward SMA carrier screening among Chinese pregnant people. In this study, pregnant women in Eastern China who were undergoing routine chromosomal screening programs were invited to view an educational video about SMA and complete a 26-item survey regarding their attitudes toward SMA screening by scanning a specific quick response code. A total of 1673 questionnaires were collected, and 81.1% of respondents were willing to undergo self-funded screening. If the screening program were included in the medical insurance, 97.8% of respondents were willing to accept screening. The important reasons for supporting SMA screening were a belief that it could help them make better reproductive decisions and avoid having a child with SMA. The key reason for declining SMA screening was not having a family history of genetic diseases. A higher score for SMA genetics knowledge was associated with a greater willingness to undergo SMA screening. We concluded that pregnant women in Eastern China had positive attitudes toward SMA carrier screening. Improving genetic knowledge and including the screening program in medical insurance would support the widespread implementation of SMA carrier screening. Steps should be taken to offer SMA carrier screening along with pre- and posttest education and genetic counseling to raise awareness and reduce misconceptions regarding SMA.

Parents as informal caregivers of children and adolescents with spinal muscular atrophy: a systematic review of quantitative and qualitative data on the psychosocial situation, caregiver burden, and family needs.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare degenerative neuromuscular disease, mostly occurring in infants and children, leading to muscle wasting and weakness, and premature death. Due to new developments of multiple disease-modifying treatments within the last years, the interest of research in patients affected by SMA increased steadily. However, the psychosocial situation of parents as informal caregivers is still rarely addressed. OBJECTIVES: This review aims to highlight quantitative and qualitative data about the psychosocial situation, caregiver burden, and needs of parents as informal caregivers for children and adolescents with SMA. METHODS: A systematic literature review was performed including quantitative and qualitative original studies focusing on different psychosocial aspects and outcomes for parents of children and adolescents < 21 years of age with SMA type I-IV (PROSPERO; registration number CRD42020219020). We searched the following databases in November 2020 with a research update in August 2021: MEDLINE, CINAHL, PsycINFO and Web of Science. RESULTS: In total, 24 articles from 23 studies were selected for inclusion (15 quantitative studies, 7 articles from 6 qualitative studies, 2 mixed methods studies). The synthesis of included studies shows multiple sources of psychosocial burden for parents of children and adolescents affected by SMA: Most studies found reduced levels of quality of life, moderate to high levels of caregiver burden and distress, as well as physical and mental health symptoms. Further, findings indicate several unmet family needs regarding information, care coordination, treatment decisions, financial support, and adequate supportive care services. CONCLUSION: Parents of children and adolescents with SMA face multiple sources of psychosocial stressors, caregiver burden and various unmet family needs. To unburden families, the needs of parents as caregivers should be included in integrated care paths for SMA to improve their psychosocial situation and thus their ability to care for their children and to treat or prevent physical and mental health problems due to overburdening. Future research should focus not only on quality of life and on caregiving-related burden but should also examine the clinical relevance of reported symptoms to support the implementation of adequate support services for families affected by SMA.

A mixed method study on the impact of living with spinal muscular atrophy in Malaysia from patients' and caregivers' perspectives.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a rare, recessively inherited neuromuscular disorder that causes progressive muscle weakness. There is a low degree of awareness about SMA amongst the public and healthcare providers, which may impact the perception of the disease and its proper management. To understand how this lack of awareness may have affected diagnosis, care and support for SMA patients and their caregivers, this study aims to investigate the impact of SMA on the lives and daily activities of SMA patients and their caregivers in Malaysia. METHODS: Nationwide recruitment was carried out via invitations coordinated by a local SMA advocacy organization. A mixed method cross-sectional study consisting of a self-administered questionnaire followed by in-depth interviews (IDIs) and focus group discussions (FGDs) was conducted. The interview sessions were audio-taped, and verbatim transcripts analyzed thematically. RESULTS: Participants reported feeling stressed, anxious and depressed. There were issues with delayed diagnosis, lack of information from healthcare professionals about the disease progression, and limited access to supportive services like physiotherapy. Participants expressed their concerns living with self-doubt and turmoil with having to modify their lifestyles, relationships with family and friends, and challenges with educational and career opportunities. Various themes of their hopes for the future touched on having access to treatment, clinical trials, holistic care for symptom management, as well as improving infrastructure for disability access. CONCLUSION: This study, to the best of our knowledge represents the first comprehensive study on SMA in South East Asia, highlights a plethora of issues and challenges experienced by persons with spinal muscular atrophy (PWSMA) and their caregivers in Malaysia, from the point of SMA diagnosis and throughout the management of care, in addition to the deep psychosocial impact of living with SMA. The significant findings of this study may contribute to a better understanding among stakeholders to make improvements in clinical practice, the education system, the work environment as well as holistic care support and society at large.

The characteristics of self-care in children with spinal muscular atrophy: an integrative review.

INTRODUCTION: Spinal muscular atrophy (SMA) is one of the most common genetic causes of death in children. Recently, European Commission (EU) has approved a new gene therapy based on onasemnogene abeparvovec (Zolgensma) for the treatment of patients with SMA. It is essential that children suffering from SMA also apply self-care methods to maintain their health, monitor their weight and food intake, and use appropriate remedies. Indeed, self-care is a crucial element in the health care system because it is able to improve survival and prevent hospitalizations. The purpose of this review is to systematically explore the characteristics of self- care in children with SMA and the relationship with their parents and the collaboration of health- care professionals. EVIDENCE ACQUISITION: An integrative review of the literature has been conducted. The electronic databases CINAHL, Embase, PubMed, and SCOPUS were searched. EVIDENCE SYNTHESIS: Thirteen articles met the inclusion criteria and were reviewed using Whittemore and Knalf's integrative review methodology. The analysis of the 13 articles selected for the review show that previous literature has focused on six prevalent themes: problem solving and care behavior, decision making, optimizing living with an illness, high quality, child-focused homecare, healthcare professionals, and monitoring behaviors. CONCLUSIONS: This paper highlights how self-management behaviors depend on four basic aspects: the person (individual, cognitive, and social perceptions), the patient's family (level of knowledge of the pathology, involvement in the management and quality of relationship with the patient), the community (relationships with external social contexts, such as school and other organizations), and the healthcare system (availability of resources and the degree of evolution of healthcare).

The Spinal Muscular Atrophy Health Index: Italian validation of a disease-specific outcome measure.

Patient report outcome measures in Spinal Muscular Atrophy (SMA) represent a potential complement to observer rated scales which can be used to better understand treatment response. We developed, translated and validated an Italian version of the Spinal Muscular Atrophy Health Index (SMAHI), a disease-specific, patient reported outcome measure questionnaire, designed to estimate the patients' perception of disease burden. Test-retest reliability was assessed in 37 patients (16 children aged 12-17 and 21 adults) and was excellent in both cohorts. Internal consistency in an additional 98 patients (24 children, 74 adults) was also excellent (Cronbach's alpha = 0.93 and 0.91 respectively). In children the highest level of disease burden was generated from lower limb dysfunction and fatigue as well as their perception of decreased performance in social situations. Most patients in the adult cohort were sitters and complained of problems with upper limb functions as well as of fatigue. The SMAHI-IT was also able to differentiate between SMA types according to diseases severity. The results of our study demonstrate that the SMAHI can be considered a marker of disease-specific burden in patients with SMA with a high test-retest reliability and internal validity in Italian patients aged 12 and older.

Understanding European patient expectations towards current therapeutic development in spinal muscular atrophy.

Following the 2017 approval of a first spinal muscular atrophy (SMA) treatment by the European Medicines Agency, SMA Europe launched a Europe-wide survey with the goal of understanding patients' treatment expectations, realities of daily living and access to clinical trials and therapy, and how this varied according to parameters such as age and disease severity. A response rate of 31% yielded 1474 completed surveys from 26 European countries. In line with findings from a 2015 SMA Europe-led survey, participants considered stabilization of their condition to be progress. Notably, responses indicated that the current classification of SMA at diagnosis by 'type' often does not reflect current mobility level. Large gaps in treatment access were identified that varied in particular between age and disease severity groups, yet there was high interest in clinical trial participation. In addition, alternative treatment options, including combination therapies, are now expectations. These perspectives should be central considerations through the research and development processes of new SMA therapies, through data generation and discussions on access to therapies. Results from this survey indicate that collaboration between stakeholders is essential to the foundation upon which innovative approaches for SMA treatments and access can be explored.

Chronic Pharmacological Increase of Neuronal Activity Improves Sensory-Motor Dysfunction in Spinal Muscular Atrophy Mice.

Dysfunction of neuronal circuits is an important determinant of neurodegenerative diseases. Synaptic dysfunction, death, and intrinsic activity of neurons are thought to contribute to the demise of normal behavior in the disease state. However, the interplay between these major pathogenic events during disease progression is poorly understood. Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by a deficiency in the ubiquitously expressed protein SMN and is characterized by motor neuron death, skeletal muscle atrophy, as well as dysfunction and loss of both central and peripheral excitatory synapses. These disease hallmarks result in an overall reduction of neuronal activity in the spinal sensory-motor circuit. Here, we show that increasing neuronal activity by chronic treatment with the FDA-approved potassium channel blocker 4-aminopyridine (4-AP) improves motor behavior in both sexes of a severe mouse model of SMA. 4-AP restores neurotransmission and number of proprioceptive synapses and neuromuscular junctions (NMJs), while having no effects on motor neuron death. In addition, 4-AP treatment with pharmacological inhibition of p53-dependent motor neuron death results in additive effects, leading to full correction of sensory-motor circuit pathology and enhanced phenotypic benefit in SMA mice. Our in vivo study reveals that 4-AP-induced increase of neuronal activity restores synaptic connectivity and function in the sensory-motor circuit to improve the SMA motor phenotype.SIGNIFICANCE STATEMENT Spinal muscular atrophy (SMA) is a neurodegenerative disease, characterized by synaptic loss, motor neuron death, and reduced neuronal activity in spinal sensory-motor circuits. However, whether these are parallel or dependent events is unclear. We show here that long-term increase of neuronal activity by the FDA-approved drug 4-aminopyridine (4-AP) rescues the number and function of central and peripheral synapses in a SMA mouse model, resulting in an improvement of the sensory-motor circuit and motor behavior. Combinatorial treatment of pharmacological inhibition of p53, which is responsible for motor neuron death and 4-AP, results in additive beneficial effects on the sensory-motor circuit in SMA. Thus, neuronal activity restores synaptic connections and improves significantly the severe SMA phenotype.

Structural and functional brain connectome in motor neuron diseases: A multicenter MRI study.

OBJECTIVE: To investigate structural and functional neural organization in amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), and progressive muscular atrophy (PMA). METHODS: A total of 173 patients with sporadic ALS, 38 patients with PLS, 28 patients with PMA, and 79 healthy controls were recruited from 3 Italian centers. Participants underwent clinical, neuropsychological, and brain MRI evaluations. Using graph analysis and connectomics, global and lobar topologic network properties and regional structural and functional brain connectivity were assessed. The association between structural and functional network organization and clinical and cognitive data was investigated. RESULTS: Compared with healthy controls, patients with ALS and patients with PLS showed altered structural global network properties, as well as local topologic alterations and decreased structural connectivity in sensorimotor, basal ganglia, frontal, and parietal areas. Patients with PMA showed preserved global structure. Patient groups did not show significant alterations of functional network topologic properties relative to controls. Increased local functional connectivity was observed in patients with ALS in the precentral, middle, and superior frontal areas, and in patients with PLS in the sensorimotor, basal ganglia, and temporal networks. In patients with ALS and patients with PLS, structural connectivity alterations correlated with motor impairment, whereas functional connectivity disruption was closely related to executive dysfunction and behavioral disturbances. CONCLUSIONS: This multicenter study showed widespread motor and extramotor network degeneration in ALS and PLS, suggesting that graph analysis and connectomics might represent a powerful approach to detect upper motor neuron degeneration, extramotor brain changes, and network reorganization associated with the disease. Network-based advanced MRI provides an objective in vivo assessment of motor neuron diseases, delivering potential prognostic markers.

Choosing Life with Spinal Muscular Atrophy Type 1.

This article is co-authored by the mother of a patient with spinal muscular atrophy (SMA), two pediatric pulmonologists and the pediatric neurologist in the team. It describes the patient and their family's experience of living with SMA. This commentary describes the mother's experience of the diagnosis and treatment process of her daughter's SMA in an era of emerging treatments for a disease which was until recently considered incurable. SMA diagnosis and management in the context of the patient mother's experiences is discussed.

"The Whole Game is Changing and You've Got Hope": Australian Perspectives on Treatment Decision Making in Spinal Muscular Atrophy.

INTRODUCTION: The natural history and treatment of spinal muscular atrophy (SMA) is currently being transformed by the development and availability of novel therapies, with significant related changes in practice. This not only has important implications for the health and wellbeing of patients with SMA and their families, as well as improves the quality of care. OBJECTIVE: The present study aimed to investigate the processes and factors that influence treatment and healthcare decisions for children and adults with SMA and their families and healthcare providers. METHODS: Four focus groups comprising adults, or parents of children and adolescents, with SMA and an expert panel of healthcare providers (N = 25) explored experiences of SMA, its treatment and related decision making and expectations for future care. Group discussions were recorded and transcribed verbatim for thematic analysis using NVivo12.0. RESULTS: People with SMA, their families and healthcare providers described confronting complex healthcare decisions in the context of a rapidly changing SMA treatment environment. Across all groups, five key themes were identified: hope, yearning and searching, patient-centred care and support, community and a sense of connectedness and weighing up potential treatment benefits and costs. Essential to these themes was the notion of what it means to live with SMA and complexities relating to 'quality of life'. CONCLUSION: Identifying and more deeply understanding the factors that influence patient, family and healthcare providers' decision making regarding SMA treatment is an important first step in improving the quality of patient- and family-centred care and in informing clinical practice and future health policy incorporating personalized medicine and optimal supportive and mental health care.

A Prospective, Crossover Survey Study of Child- and Proxy-Reported Quality of Life According to Spinal Muscular Atrophy Type and Medical Interventions.

BACKGROUND: Spinal muscular atrophy is an autosomal-recessive, progressive neuromuscular disease associated with extensive morbidity. Children with spinal muscular atrophy have potentially increased life spans due to improved nutrition, respiratory support, and novel pharmaceuticals. OBJECTIVES: To report on the quality of life and family experience for children with spinal muscular atrophy with attentiveness to patient- and proxy-concordance and to stratify quality of life reports by spinal muscular atrophy type and medical interventions. METHODS: A prospective, crossover survey study inclusive of 58 children (26 spinal muscular atrophy type I, 23 type II, 9 type III) and their family caregivers at a free-standing Midwestern children's hospital. Twenty-eight families completed the 25-item PedsQL 3.0 Neuromuscular Module. Forty-four participants completed the 36-item PedsQL Family Impact Module and 47 completed the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire. RESULTS: The PedsQL Family Impact Module demonstrated significant differences between spinal muscular atrophy types I and II in functioning domains including physical, emotional, social, and family relations (P < .03). Child self-report and proxy report surveys demonstrated significant differences between spinal muscular atrophy types in the communication domains (P < .003). Children self-reported their quality of life higher than proxy report of child quality of life. Gastrostomy tube (P = .001) and ventilation support (P = .029) impacted proxy-reported quality of life perspectives, whereas nusinersen use did not. Spinal surgery was associated with improved parental quality of life and family impact (P < .03). CONCLUSIONS: The measurement and monitoring of quality of life for children with spinal muscular atrophy and their families represents an implementable priority for care teams.

A critical review of patient and parent caregiver oriented tools to assess health-related quality of life, activity of daily living and caregiver burden in spinal muscular atrophy.

The positive outcome of different therapeutic approaches for spinal muscular atrophy (SMA) in clinical trials and in clinical practice have highlighted the need to establish if functional changes are associated with possible changes of patient health-related quality of life or have an effect on activities of daily living and caregiver burden. The aim of this paper is to provide a critical review of the tools previously or currently used to measure quality of life, activity of daily living, and caregiver burden in SMA. We identified 36 measures. Only 6 tools were specifically developed for SMA while the others had been used and at least partially validated in wider groups of neuromuscular disorders including SMA. Twelve of the 36 focused on health-related quality of life, 5 on activities of daily living and 9 on caregiver burden. Ten included a combination of items. The review provides a roadmap of the different tools indicating their suitability for different SMA types or age groups. Scales assessing activities of daily living and care burden can provide patients and carers perspective on functional changes over time that should be added to the observer rated scales used in clinic.

User perspectives on a psychosocial blended support program for partners of patients with amyotrophic lateral sclerosis and progressive muscular atrophy: a qualitative study.

BACKGROUND: Partners are often the main caregivers in the care for patients with amyotrophic lateral sclerosis (ALS) and progressive muscular atrophy (PMA). Providing care during the progressive and fatal disease course of these patients is challenging and many caregivers experience feelings of distress. A blended psychosocial support program based on Acceptance and Commitment Therapy was developed to support partners of patients with ALS and PMA. The aim of this qualitative study is to gather insight into experiences with different components of the support program (program evaluation) and to discover what caregivers gained from following the program (mechanisms of impact). METHODS: Individual in-depth interviews, about caregivers' experiences with the support program were conducted with 23 caregivers of ALS/PMA patients enrolled in a randomized controlled trial designed to measure the effectiveness of the blended psychosocial support program. The program, performed under the guidance of a psychologist, consists of psychoeducation, psychological and mindfulness exercises, practical tips and information, and options for peer contact. Interviews were audio-recorded, transcribed verbatim and analyzed thematically. RESULTS: The program evaluation showed that caregivers perceived each component of the program as beneficial but ambivalent reactions were expressed about the mindfulness exercises and peer contact functions. Caregivers expressed the need for a more personalized program with respect to the order and timing of the modules and wanted to continue the support program for a longer time. The main mechanism of impact of the program that caregivers reported was that they became more aware of their own situation. They further indicated that the program helped them to perceive control over the caregiving situation, to accept negative emotions and thoughts, to be there for their partner and feel acknowledged. CONCLUSIONS: The blended psychosocial support program for caregivers of patients with ALS/PMA is valued by caregivers for enhancing self-reflection on their challenging situation which stimulated them to make choices in line with their own needs and increased their feeling of control over caregiving. The different components of the program were overall appreciated by caregivers, but the mindfulness and peer support components should be further adapted to the needs of the caregivers. TRIAL REGISTRATION: Dutch Trialregister NTR5734 , registered 28 March 2016.

Advance care planning in progressive neurological diseases: lessons from ALS.

BACKGROUND: There is increasing awareness of the need for an integrated palliative care approach in chronic progressive neurological diseases. Advance care planning (ACP) is an integral part of this approach. As a systematically organized and ongoing communication process about patients' values, goals and preferences regarding medical care during serious and chronic illness, ACP aims to involve patients in decision-making before they become cognitively and communicatively incapable. However, it remains underutilized in daily neurological practice except for speciality clinics such as ALS centers. Our aim was to study ACP in the tertiary ALS center Amsterdam and to investigate patients' reflections on it. Subsequently we used this knowledge to formulate recommendations for integration of ACP in the care of patients with other chronic progressive neurological diseases. METHODS: Non-participating observations of all appointments of patients with amyotrophic lateral sclerosis (ALS) or progressive muscular atrophy (PMA) with the treating physician, in various stages of disease, during 6 consecutive months, followed by single in-depth interviews, and an inductive analysis. RESULTS: Twenty-eight Dutch patients participated, varying in age, gender, disease onset and severity of physical decline. ACP started directly when the diagnosis was given, by means of a general outlook on the future with progressive disability and immediate introduction to a customized multidisciplinary team. During follow-up ACP was realized by regular appointments in which monitoring of the patient's status and clear communication strategies formed the basis of tailor-made discussions on treatment options. Patients accepted this policy as careful professional guidance. CONCLUSIONS: ACP is a professional communication process throughout the whole course of progressive disease. It is feasible to integrate ACP into follow-up of patients with ALS and PMA from diagnosis onwards. Supported by recent literature, we argue that such a well-structured approach would also enhance the quality of care and life of patients with other chronic progressive neurological diseases.

"Getting ready for the adult world": how adults with spinal muscular atrophy perceive and experience healthcare, transition and well-being.

BACKGROUND: Spinal muscular atrophy (SMA) has profound implications across a lifetime for people with the condition and their families. Those affected need long-term multidisciplinary medical and supportive care to maintain functional mobility, independence and quality of life. Little is known about how adults with SMA experience healthcare, or the components of care perceived as important in promoting well-being. The purpose of this study was to use qualitative research methodology to explore the lived experiences of healthcare and wellbeing of adults with SMA. Purposive sampling was used to recruit adolescents and adults with SMA, their parents and partners. Face-to-face or telephone-based semi-structured interviews were recorded and analysed using inductive thematic analysis. RESULTS: Across a total of 25 interviews (19 people with SMA, 5 parents, 1 partner) many participants described disengagement from health services and major gaps in care throughout adulthood. Disengagement was attributed to the perceived low value of care, as well as pragmatic, financial and social barriers to navigating the complex healthcare system and accessing disability services. Adults with SMA valued healthcare services that set collaborative goals, and resources with a positive impact on their quality of life. Mental health care was highlighted as a major unmet need, particularly during times of fear and frustration in response to loss of function, social isolation, stigma, and questions of self-worth. Alongside this, participants reported resilience and pride in their coping approaches, particularly when supported by informal networks of family, friends and peers with SMA. CONCLUSIONS: These findings provide insight into the lived experiences, values and perspectives of adults with SMA and their carers, revealing major, ongoing unmet healthcare needs, despite many realising meaningful and productive lives. Findings indicate the necessity of accessible, patient- and family-centered multidisciplinary care clinics that address currently unmet physical and mental health needs. Understanding the lived experiences of people with SMA, particularly during times of transition, is critical to advancing health policy, practice and research. Future studies are needed to quantify the prevalence, burden and impact of mental health needs whilst also exploring potential supportive and therapeutic strategies.

Cognitive and behavioural changes in PLS and PMA:challenging the concept of restricted phenotypes.

OBJECTIVES: Cognitive and behavioural changes within the spectrum of frontotemporal dementia (FTD) are observed frequently in patients with amyotrophic lateral sclerosis (ALS). Whether these changes also occur in other forms of motor neuron disease (MND) is not well studied. We therefore systemically screened a large cohort of patients with primary lateral sclerosis (PLS) and progressive muscular atrophy (PMA) for cognitive and behavioural changes, and subsequently compared our findings with a cohort of patients with ALS. METHODS: Using a set of screening instruments (Edinburgh Cognitive and Behavioural ALS Screen, ALS and Frontotemporal Dementia Questionnaire, Frontal Assessment Battery, and Hospital Anxiety and Depression Scale), the presence of cognitive and behavioural changes as well as anxiety and depression in 277 patients with ALS, 75 patients with PLS and 143 patients with PMA was evaluated retrospectively. RESULTS: We found a high frequency of cognitive and behavioural abnormalities with similar profiles in all three groups. Subjects with behavioural variant FTD were identified in all groups. CONCLUSIONS: The percentage of patients with PLS and PMA with cognitive dysfunction was similar to patients with ALS, emphasising the importance for cognitive screening as part of routine clinical care in all three patient groups. With a similar cognitive profile, in line with genetic and clinical overlap between the MNDs, the view of PLS as an MND exclusively affecting upper motor neurons and PMA exclusively affecting lower motor neurons cannot be held. Therefore, our findings are in contrast to the recently revised El Escorial criteria of 2015, where PLS and PMA are described as restricted phenotypes. Our study favours a view of PLS and PMA as multidomain diseases similar to ALS.

Perceived Fatigue in Spinal Muscular Atrophy: A Pilot Study.

BACKGROUND: Fatigue is a common complaint in spinal muscular atrophy (SMA). Fatigability is well described in ambulatory SMA but the relationship to perceived fatigue has not been evaluated. Understanding this relationship has proven challenging for most disorders. OBJECTIVE: To assess the relationship of perceived fatigue to fatigability, function, and quality of life in SMA. METHODS: Thirty-two participants with SMA (21.9% type 2, 78.1% type 3) were recruited. Perceived fatigue and fatigability, function, and quality of life were assessed using standardized questionnaires and assessments. Associations were analyzed using Pearson correlation coefficients (p = 0.05). Also, the effects of age, type, and ambulatory status were determined on perceived fatigue. RESULTS: All SMA participants reported fatigue. Perceived fatigue was not associated with function, quality of life, or fatigability in ambulatory SMA patients. Neither age, type, nor ambulatory status influenced perceived fatigue. CONCLUSIONS: Perceived fatigue can be quantified in SMA. Interestingly, perceived fatigue did not correlate with fatigability or function, suggesting that cognitive, homeostatic, or psychologic factors may be more relevant as co-morbid factors. Clinical trials targeting perceived fatigue in SMA should focus on these patient-reported assessments. A multilevel approach is required to separate the various mechanisms involved in perceived fatigue.