Patient-Reported Outcome Measures in Neuromuscular Diseases: A Scoping Review.

 Patient-reported outcome measures (PROMs) are valuable in comprehensively understanding patients' health experiences and informing healthcare decisions in research and clinical care without clinicians' input. Until now, no central resource containing information on all PROMS in neuromuscular diseases (NMD) is available, hindering the comparison and choice of PROMs used to monitor NMDs and appropriately reflect the patient's voice. This scoping review aimed to present a comprehensive assessment of the existing literature on using PROMs in children and adults with NMD. A scoping methodology was followed using Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines to assess the literature on PROMs in NMDs. Eligibility criteria encompassed articles describing psychometric development or evaluation of generic or disease-specific PROM-based instruments for adults and children with specific NMDs. The data charting process involved extracting measurement properties of included PROMs, comprising validity, reliability, responsiveness, and interpretability information. The review identified 190 PROMs evaluated across 247 studies in individuals with NMDs. The majority of PROMs were disease specific. The physical functioning domain was most assessed. Validity was the most frequently investigated measurement property, with a limited number of PROMs sufficiently evaluated for a range of psychometric characteristics. There is a strong need for further research on the responsiveness and interpretability of PROMs and the development of PROMs on social functioning in NMD.

267th ENMC International workshop: psychological interventions for improving quality of life in slowly progressive neuromuscular disorders.

This workshop aimed to develop recommendations for psychological interventions to support people living with slowly progressive neuromuscular disorders (NMD). The workshop comprised clinicians, researchers, people living with NMD and their relatives. First, participants considered the key psychological challenges presented by NMD and the impact of NMD on relationships and mental health. Later, several psychological approaches for enhancing well-being in NMD were described. The results of randomised controlled trials of Cognitive Behaviour Therapy and Acceptance and Commitment Therapy for improving fatigue, quality of life, and mood in adults with NMD were examined. Then the group considered ways to adapt therapies for cognitive impairments or neurodevelopmental differences that occur in some NMD, alongside ways to support children and adolescents with NMD and their family members. Based on the evidence from randomised controlled trials, carefully conducted observational studies, and the coherence of these data with the experience of those living with NMD, the group recommends that psychological interventions should be embedded in the routine clinical care offered to people living with NMD.

Do classical and computerized cognitive tests have equal intrarater reliability in myotonic dystrophy type 1?

Myotonic dystrophy type 1 (DM1) is a multisystemic inherited neuromuscular disease leading to central nervous system symptoms, including cognitive impairments, among multiple other symptoms. However, information is presently lacking regarding the psychometric properties of neuropsychological tests and promising computerized cognitive tests, such as the Cambridge Neuropsychological Test Automated Battery (CANTABⓇ). This type of information is critical to improve clinical trial readiness and provide knowledge of DM1 natural history. The aims of the present study were (1) to document the intrarater reliability of classic paper-pencil tests assessing visuospatial working memory, cognitive flexibility, attention, episodic memory and apathy, and (2) to compare these findings with their equivalent computerized automated tests from the CANTABⓇ. Thirty participants were seen twice at four-week intervals. Results showed that the Stroop Color and Word Test (ICC = 0.741-0.869) and the Ruff 2 & 7 (ICC = 0.703-0.871) appear to be reliable paper-and-pencil tests in the DM1 population. For the CANTABⓇ, a similar observation was made for the Multitasking test (ICC = 0.588-0.792). Further studies should explore the applicability and concurrent validity of the CANTAB® and classic neuropsychological assessments in additional cohorts of DM1 patients.

Impact of a 12-week Strength Training Program on Fatigue, Daytime Sleepiness, and Apathy in Men with Myotonic Dystrophy Type 1.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular disorder causing a plea of impairments, of which fatigue and apathy are some of the most frequent non-muscular symptoms. No curative treatment exists to date, and patients only have access to limited effective care, which are intended to decrease the burden of specific symptoms in daily life. OBJECTIVE: This study aimed to assess whether a 12-week strength training program has an impact on fatigue/daytime sleepiness, apathy, and disease bruden in men with DM1. METHODS: Eleven participants completed the Fatigue and Daytime Sleepiness Scale (FDSS) and the Myotonic Dystrophy Health Index (MDHI) at baseline, at 6 and 12 weeks, and at 6 and 9 months. Also, the Apathy Evaluation Scale (AES) was filled out at baseline, at 12 weeks, and at 6 and 9 months. RESULTS: Results show significant effects of the training program both on apathy and fatigue/daytime sleepiness, effects that are respectively greater at three and six months after the end of the program than at its very end. However, no difference was observed regarding the overall disease burden. CONCLUSION: These findings are promising for patients with DM1 considering that few non-pharmacological treatments are available.

Instrumental activities of daily living in adults with the DM1 childhood phenotype: going beyond motor impairments.

Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy among adults. This cross-sectional study documents the level of independence in the instrumental activities of daily living (IADL) and explores the impact of executive functions and apathy on IADL accomplishment level among adults with the childhood phenotype of DM1. IADL accomplishment level was assessed with the Independent Living Scale (ILS) and the Activities of Daily Living Profile (ADL Profile). The later considered four operations related to executive functions: formulating a goal, planning, carrying out the task and goal attainment. Thirty-three individuals (19 females; mean age 39y, standard deviation 10y 6mo; range 23-57y) were recruited. According to the ILS total score, half of the participants were categorised as dependent. In financial management, no participant obtained the minimal score for independence. In the ADL Profile, higher dependence levels were frequent in IADL. Formulating a goal was the most difficult operation. Dependence level was more frequent in participants with apathy. Adults with the childhood phenotype exhibit significant difficulties in IADL accomplishment, especially considering their age. High levels of dependency observed with both outcome measures highlight their need for services to achieve optimal living conditions.

Predictors of participation restriction over a 9-year period in adults with myotonic dystrophy type 1.

PURPOSE: For slowly progressive neuromuscular disease, prognostic approach and long-term monitoring of participation is a crucial part of rehabilitation services. To improve the prognostic approach, professionals must identify individuals at risk of having higher participation restriction. This study aimed to identify personal and environmental predictors of participation restriction over nine years in adults with myotonic dystrophy type 1 (DM1). METHODS: A secondary analysis of a longitudinal design comparing baseline with a follow-up nine years later was used with a multidimensional assessment of participation and personal and environmental factors. Based on theoretical models, multiple linear regressions were used. RESULTS: One hundred and fourteen adults with DM1 were included in the study (63.2% women; 78.9% adult onset; mean (SD) age of 43.5 (10.4) years). When age, sex, phenotype, and education were controlled for, participation restriction was predicted by a longer time to stand and walk, lower grip strength, higher body mass index, absence of perceived impact of myotonia in daily living, use of adapted transportation from community services, and perception of obstacle in physical environment (p < 0.001, adjusted R2 = 0.50). CONCLUSIONS: The majority of predictors of participation restriction can be advantageously modified by rehabilitation and environmental changes, such as politics targeting community services provision or physical environment and services accessibility.Implications for rehabilitationPredictors could better inform rehabilitation professional to recognize individuals at risk of higher participation restriction over time and to target specific interventions based on a prognostic approach.Rehabilitation professionals could inform the people living with myotonic dystrophy type 1 and their relatives of the multifactorial nature of occurrence of participation restriction to diminish the "fatality" associated with a genetic progressive disorder.Predictors allow professionals to assess and intervene in the management of specific factors depending on the rehabilitation goal.Identifying individual with myotonic dystrophy with higher risk of participation restriction could help implement a long-term community based rehabilitation intervention plan targeting both personal and environmental factors.

Responsiveness of Daytime Sleepiness and Fatigue Scales in Myotonic Dystrophy Type 1.

Daytime sleepiness and fatigue are prominent symptoms of myotonic dystrophy type 1 (DM1) that can be amenable to treatment in the context of randomized controlled trials. No study has yet documented whether self-reported measures of daytime sleepiness and fatigue can detect change over time and the meaning of this change. The aim was to explore indicators of responsiveness to change and interpretability for the Daytime Sleepiness Scale and the Fatigue Severity Scale in 115 DM1 prospectively followed patients. Results suggest that these two self-reported questionnaires are sufficiently sensitive to detect changes beyond expected measurement error over time in this population.

Accomplishment of instrumental activities of daily living and its relationship with cognitive functions in adults with myotonic dystrophy type 1 childhood phenotype: an exploratory study.

BACKGROUND: The childhood phenotype of myotonic dystrophy type 1 (DM1) involves impaired cognitive functioning starting in infancy, which may compromise later on their ability to carry out instrumental activities of daily living (IADLs) necessary for living independently. The current study aims to document the ability to perform IADLs among adults with the childhood phenotype of DM1 and to explore its links to cognitive functioning. METHODS: This cross-sectional exploratory study was conducted among 11 individuals living with DM1. IADLs related to money management, home management & transportation and health & safety activities were assessed by the Independent Living Scale (ILS). Neuropsychological tests assessed participants' intellectual abilities and executive functioning. Associations were investigated using Spearman's rho correlation. RESULTS: Important difficulties were found in all three categories of IADLs, mostly in money management in which only 2/11 participants were scored as independent. 8/11 participants showed low to very low intellectual functioning and limit to impaired executive functioning. Apathy was also a common feature as 5/11 participants showed clinical level of apathy. A lower IQ was associated with greater difficulty in the home management & transportation subtest of the ILS. CONCLUSIONS: Adults with the childhood phenotype of DM1 demonstrate relative dependence in regard to the following IADLs: money management and home management & transportation. Level of dependence is, at least partially, associated with cognitive impairments. The work relates to results from an exploratory study; thus, studies must be pursued to describe in more details difficulties experienced by this population.

DNA methylation at the DMPK gene locus is associated with cognitive functions in myotonic dystrophy type 1.

Aim: Myotonic dystrophy type 1 (DM1) is caused by an unstable trinucleotide (CTG) expansion at the DMPK gene locus. Cognitive dysfunctions are often observed in the condition. We investigated the association between DMPK blood DNA methylation (DNAm) and cognitive functions in DM1, considering expansion length and variant repeats (VRs). Method: Data were obtained from 115 adult-onset DM1 patients. Molecular analyses consisted of pyrosequencing, small pool PCR and Southern blot hybridization. Cognitive functions were assessed by validated neuropsychological tests. Results: For patients without VRs (n = 103), blood DNAm at baseline independently contributed to predict cognitive functions 9 years later. Patients with VRs (n = 12) had different DNAm and cognitive profiles. Conclusion: DNAm allows to better understand DM1-related cognitive dysfunction etiology.

Predicting daytime sleepiness and fatigue: a 9-year prospective study in myotonic dystrophy type 1.

OBJECTIVE: Daytime sleepiness and fatigue are prominent symptoms of myotonic dystrophy type I (DM1) that exact a heavy toll on patients' quality of life, but information is scarce on their predictive factors. This study aimed to determine factors that may influence levels of daytime sleepiness and fatigue in a large cohort of DM1 patients followed for 9 years. METHODS: This study included 115 patients with DM1 at baseline (Time 1, T1) and at Time 2 (T2) who were questioned for daytime sleepiness, fatigue, history of depression, psychological distress, pain, hypothyroidism, and sleep habits. Also, their muscular impairment and intellectual quotient were evaluated. Regression models were used to identify correlates of daytime sleepiness and fatigue while controlling for time effect. RESULTS: Both daytime sleepiness and fatigue increased between T1 and T2, but their rate of change are higher when CTG repeat number is higher (p < 0.05). Also, higher psychological distress level is associated with higher daytime sleepiness and fatigue levels both at T1 and T2 (p < 0.01). Moreover, patients with a history of depression report higher daytime sleepiness levels both at T1 and T2 (p < 0.05). In addition, patients with higher fatigue levels both at T1 and T2 have more severe muscular impairment (p < 0.01) and report a longer habitual sleep duration (p < 0.05). Finally, a higher BMI and a history of hypothyroidism predict higher daytime sleepiness levels at T2 (p < 0.05). CONCLUSION: This study identified potentially modifiable risk factors of future daytime sleepiness and fatigue in DM1 patients, including BMI, psychological distress, hypothyroidism, and sleep habits.

Consensus-based care recommendations for adults with myotonic dystrophy type 1.

PURPOSE OF REVIEW: Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit. RECENT FINDINGS: The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page Quick Reference Guide and a comprehensive, 55-page document that provides clinical care recommendations for 19 discrete body systems and/or care considerations. SUMMARY: The resulting recommendations are intended to help standardize and elevate care for this patient population and reduce variability in clinical trial and study environments.

A Review of Psychopathology Features, Personality, and Coping in Myotonic Dystrophy Type 1.

BACKGROUND: The last literature review on psychopathological features in Myotonic Dystrophy type 1 had been conducted by Ambrosini and Nurnberg in 1979. Since that date, many researches had been carried out. OBJECTIVE: The aim of this study is (i) to systematically obtain and evaluate the relevant literature on psychopathological features, personality, and coping in individuals with adult phenotypes of Myotonic Dystrophy type 1. (ii) To summarize current research findings and draw conclusions for future research. METHODS: A systematic search was conducted on Pubmed, PubPsych, PsycInfo, Science Direct, and Scopus covering the period of January 1979 to July 2017. RESULTS: In view of our literature review, patients show mild psychopathological problems, such as interpersonal difficulties, lack of interest, dysphoria, concern about bodily functioning, and hypersensibility. However, they do not experience more psychiatric disorder in comparison to the general population, except for personality disorders and depression. We discussed problems concerning depression's assessment tool. Patients also present symptoms of several personality disorders: avoidant personality disorder was the most common. Finally, coping strategies relative to limitations resulting from their disease have a negative impact on their quality of life. CONCLUSIONS: In conclusion, Myotonic Dystrophy type 1 patients did not present homogeneous psychopathological and psychological features. However, based on tendencies observed among Myotonic Dystrophy type 1 patients, elements to conceptualize their social difficulties are provided.

Reliability of the Apathy Evaluation Scale in Myotonic Dystrophy Type 1.

BACKGROUND: Apathy is a common debilitating symptom of myotonic dystrophy type 1 (DM1). The Apathy Evaluation Scale (AES) has been identified as a promising measurement instrument to be used in DM1 but its metrological properties must be further documented. OBJECTIVE: To determine the internal consistency of the Self (AES-S), Informant (AES-I), and Clinician (AES-C) versions of the AES and to assess the test-retest reliability, standard error of measurement, and minimal detectable change of the AES-S and AES-I in a sample of DM1 patients and their related informants. RESULTS: All scales showed good internal consistency (Cronbach's alpha: 0.83-0.87) and the AES-S and AES-I showed good test-retest reliability (ICC = 0.79-0.91). Additionally, clinicians and informants had a tendency to overestimate DM1 patients' level of apathy compared to patients' self-ratings, suggesting potentially impaired self-awareness in DM1 patients. CONCLUSIONS: The present results advocate the use of the AES-I as a reliable instrument to estimate apathy in DM1 patients for either clinical or research purposes, and support the relevance to pursue the assessment of metrological properties of the AES as a tool of great value for the development of outcomes for clinical trial readiness in DM1.

Further evidence for the reliability and validity of the Fatigue and Daytime Sleepiness Scale.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disease causing, among other symptoms, fatigue and excessive daytime sleepiness, which are frequently undifferentiated by patients and/or clinicians. The Fatigue and Daytime Sleepiness Scale (FDSS) has been devised to measure these two overlapping symptoms as a single clinical entity. OBJECTIVE: To further examine the reliability and the construct validity of the FDSS in patients with DM1. METHODS: The scale was administered to 48 DM1 patients on two occasions at a 2week-interval. Intra-rater reliability and internal consistency were established by calculating the intraclass correlation coefficient (ICC) and Cronbach's alpha, respectively. Construct validity was assessed by using the known-group method. More precisely, the mean FDSS score of patients with and without subjective complaints of fatigue and/or sleepiness was compared. RESULTS: The FDSS showed good intra-rater reliability (ICC=0.83) and acceptable internal consistency (Cronbach's alpha =0.6). Also, the FDSS was able to distinguish between patients who had fatigue and sleepiness complaints from those who did not (mean FDSS score of 10.6 vs 8.0, p=0.01), suggesting good construct validity. CONCLUSION: Overall, the present study supports the continued use of the FDSS as a reliable and valid instrument to measure fatigue and daytime sleepiness in patients with DM1 for either clinical or research purposes.

Cognitive decline over time in adults with myotonic dystrophy type 1: A 9-year longitudinal study.

Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disease with multisystemic involvement including the central nervous system. The evolution of the cognitive profile is a matter of debate, whether an eventual decline could be global or process-specific. Study aims are to describe, compare and document the clinical relevance of the progression of cognitive abilities in DM1 patients with adult and late-onset phenotypes. A total of 115 DM1 patients (90 adult; 25 late-onset) were assessed twice within a 9-year period on cognitive abilities (language, memory, visual attention, processing speed, visuoconstructive abilities and executive functions) and intellectual functioning (WAIS-R 7). A significant worsening over time was observed for verbal memory, visual attention, and processing speed. The progression in cognitive scores correlated with age and disease duration, but not with nCTG, muscular impairment nor education at baseline. Intellectual functioning remained stable. The rate of decline was higher among the late-onset phenotype than in the adult phenotype. Results showed that executive functions, language, and visual memory are impaired earlier in adult life, while verbal memory, visual attention, and processing speed decline later. Globally, results suggest an early and accelerated normal ageing process. This longitudinal study was based on the largest sample and the longest time period studied to date. These findings are highly relevant for clinical practice and genetic counselling.

Prevalence and correlates of apathy in myotonic dystrophy type 1.

BACKGROUND: Apathy in DM1 has long been acknowledged in clinical practice. However, a major drawback is that the concept has been only sparsely explored in previous specific studies. This study aimed to determine the prevalence of apathy in myotonic dystrophy (DM1), to compare it with facioscapulohumeral dystrophy (FSHD) patients and normal healthy controls, and explore its relationship to psychopathological features and cognitive function. METHODS: Levels of apathy in 38 DM1 patients with adult phenotypes were compared with 19 patients with FSHD and 20 matched controls. Patient participants were consecutively recruited, regarding their interdisciplinary annual evaluation at the neuromuscular pathology reference center (Institute of Myology, Paris, France), within an 18-month period. Additional measurements included motor disability, fatigue, depression, anxiety, and cognitive abilities. Inter-group comparisons were performed using non-parametric Kruskal-Wallis tests and Mann-Whitney U Tests. Intra-group comparisons were carried out with the Wilcoxon Signed rank and Friedman tests. Also, Spearman's correlations were used to assess the strength of linear relationships between pairs of variables. The significance level was set at 0.05. RESULTS: Global score of apathy was significantly higher in DM1 patients than in FSHD patients (p < 0.01) and in controls (p < 0.001). Sixteen of 38 DM1 patients (39.5 %) met the criterion for apathy, contrasting with only 4 of the 19 (21.1 %) FSHD patients. No control subject was apathetic. Moreover, apathy in DM1 patients was negatively correlated to MMSE (r = -.46, p < .05) and Stroop Word (r = -.55, p < .01) scores, but not with age, educational level, disease duration, CTG repeats, motor functional disability, fatigue, depression, and anxiety. CONCLUSIONS: Apathy is a frequent symptom in DM1 (almost 40 %). It is more prevalent than in a similarly disabled group of patients with FSHD and in controls. Results also show that apathy in DM1 is independent of the psychopathological domain, fatigue, age, and motor disability, but associated to general cognitive status. These results altogether could suggest a central cause for apathy in DM1 rather than an adjustment process to cope with the progressive and debilitating nature of the disease. Data emphasize the importance to evaluate this symptom in routine clinical management of DM1 patients.

Construction of a Quality of Life Questionnaire for slowly progressive neuromuscular disease.

PURPOSE: To build a questionnaire to assess health-related quality of life (HRQL) in patients suffering from slowly progressive neuromuscular disease (NMD) using item response theory (IRT). METHODS: A pool of 64 items and a validated questionnaire (WHOQOL-BREF) were administered to 159 patients recruited in eight NMD referral centers. Exploratory statistical analysis included methods derived from both IRT and classical test theory. RESULTS: We constructed a questionnaire named QoL-NMD which is composed of two general items and 24 items classified in three domains: (1) "Impact of Physical Symptoms," (2) "Self-perception" and (3) "Activities and Social Participation." Each domain has good psychometric properties (Cronbach's alpha > 0.77, test-retest ICC > 0.81, Loevinger's H > 0.41) and meets IRT assumptions. Comparison with the WHOQOL-BREF enabled assessing similarities and discrepancies with a generic questionnaire. CONCLUSION: This study enabled the development of a new HRQL questionnaire specifically designed for slowly progressive NMD patients. The QoL-NMD is short enough to be used in clinical practice (26 items). The next steps will be to validate QoL-NMD by re-assessing psychometrics in an independent sample of patients and calibrate the IRT scoring system.

Cognitive Deficits Associated with Sleep Apnea in Myotonic Dystrophy Type 1.

Although sleep-disordered breathing and cognitive impairment are common features of patients with myotonic dystrophy type 1 (DM1), little is known about their relationship. Forty-three adult DM1 patients underwent 2 sequential polysomnographic sessions and a neuropsychological test battery (intellectual functioning, attention, language, memory, and executive functions). Lower scores in attention, vigilance, and executive functioning tests were associated with higher number of apneic/hypopneic episodes per hour of sleep and longer total sleep time at an oxyhemoglobin saturation of less than 90%. Results suggest a potential role for nighttime breathing problems in the cognitive impairment often observed in DM1 patients.