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OBJECTIVE: The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them. METHODS: Subitem-level correlation and distribution-based analysis of 1,637 SARA assessments in 884 patients with autosomal recessive/early onset ataxia (370 with 2-8 longitudinal assessments) were complemented by linear mixed effects modeling to estimate progression and sample sizes. RESULTS: Although SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA < 25). Responsiveness was diminished by incomplete subscale use at intermediate or upper levels, nontransitions ("static periods"), and fluctuating decreases/increases. All subitems except nose-finger showed moderate-to-strong correlations to activities of daily living, indicating that metric properties-not content validity-limit SARA responsiveness. SARA captured mild-to-moderate progression in many genotypes (eg, SYNE1-ataxia: 0.55 points/yr, ataxia with oculomotor apraxia type 2: 1.14 points/yr, POLG-ataxia: 1.56 points/yr), but no change in others (autosomal recessive spastic ataxia of Charlevoix-Saguenay, COQ8A-ataxia). Whereas sensitivity to change was optimal in mild ataxia (SARA < 10), it substantially deteriorated in advanced ataxia (SARA > 25; 2.7-fold sample size). Use of a novel rank-optimized SARA without subitems finger-chase and nose-finger reduces sample sizes by 20 to 25%. INTERPRETATION: This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design. ANN NEUROL 2023;94:470-485.
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Ataxia Cerebelar , Ataxias Espinocerebelares , Humanos , Atividades Cotidianas , Ataxia , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , Extremidade SuperiorRESUMO
BACKGROUND: With treatment trials on the horizon, this study aimed to identify candidate digital-motor gait outcomes for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), capturable by wearable sensors with multicenter validity, and ideally also ecological validity during free walking outside laboratory settings. METHODS: Cross-sectional multicenter study (four centers), with gait assessments in 36 subjects (18 ARSACS patients; 18 controls) using three body-worn sensors (Opal, APDM) in laboratory settings and free walking in public spaces. Sensor gait measures were analyzed for discriminative validity from controls, and for convergent (ie, clinical and patient relevance) validity by correlations with SPRSmobility (primary outcome) and Scale for the Assessment and Rating of Ataxia (SARA), Spastic Paraplegia Rating Scale (SPRS), and activities of daily living subscore of the Friedreich Ataxia Rating Scale (FARS-ADL) (exploratory outcomes). RESULTS: Of 30 hypothesis-based digital gait measures, 14 measures discriminated ARSACS patients from controls with large effect sizes (|Cliff's δ| > 0.8) in laboratory settings, with strongest discrimination by measures of spatiotemporal variability Lateral Step Deviation (δ = 0.98), SPcmp (δ = 0.94), and Swing CV (δ = 0.93). Large correlations with the SPRSmobility were observed for Swing CV (Spearman's ρ = 0.84), Speed (ρ = -0.63), and Harmonic Ratio V (ρ = -0.62). During supervised free walking in a public space, 11/30 gait measures discriminated ARSACS from controls with large effect sizes. Large correlations with SPRSmobility were here observed for Swing CV (ρ = 0.78) and Speed (ρ = -0.69), without reductions in effect sizes compared with laboratory settings. CONCLUSIONS: We identified a promising set of digital-motor candidate gait outcomes for ARSACS, applicable in multicenter settings, correlating with patient-relevant health aspects, and with high validity also outside laboratory settings, thus simulating real-life walking with higher ecological validity. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Autosomal recessive cerebellar ataxias (ARCAs) are inherited neurological disorders that can affect both the central and peripheral nervous systems. To assess the effects of interventions according to the perception of people affected, patient-reported outcome measures (PROMs) must be available. This paper presents the development process of the Person-Reported Ataxia Impact Scale (PRAIS), a new PROM in recessive ataxias, and the documentation of its content validity, interpretability, and construct validity (structural and discriminant). The development followed the PROMIS framework and the Food and Drug Administration guidelines. A mixed-method study design was used to develop the PROM. A systematic review of the literature, semistructured interviews, and discussion groups was conducted to constitute an item pool. Experts' consultation helped formulate items, and the questionnaire was sent online to be completed by people affected. Statistical analyses were performed to assess the structural and discriminant validity. A total of 125 people affected by recessive ataxia completed the questionnaire. The factor analysis confirmed the three components: physical functions and activities, mental functions, and social functions. The statistical analysis showed that it can discriminate between stages of mobility and level of autonomy. It showed very good levels of internal consistency (0.79 to 0.89). The Person-Reported Ataxia Impact Scale (PRAIS) is a 38-item questionnaire that assesses the manifestations and impacts of the disease according to the perception of people affected by recessive ataxia. It can be used in clinical and research settings.
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Ataxia Cerebelar , Humanos , Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/genética , Medidas de Resultados Relatados pelo Paciente , Inquéritos e QuestionáriosRESUMO
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurologic disorder with generally well-known clinical manifestations. However, few studies assessed their progression rate using a longitudinal design. This study aimed to document the natural history of ARSACS over a 4-year period in terms of upper and lower limb functions, balance, walking capacity, performance in daily living activities, and disease severity. Forty participants were assessed on three occasions over 4 years. Participant performance was reported in raw data as well as in percentage from reference values to consider the normal aging process. Severe balance and walking capacity impairments were found, with a significant performance decrease over the 4 years. Balance reached a floor score of around 6 points on the Berg Balance Scale for participants aged >40 years, while other participants lost about 1.5 points per year. The mean loss in walking speed was 0.044 m/s per year and the mean decrease in the distance walked in 6 min was 20.8 m per year for the whole cohort. Pinch strength, balance, walking speed, and walking distance decreased over time even when reported in percentage from reference values. Major impairments and rapid progression rates were documented in the present study for upper limb coordination, pinch strength, balance, and walking capacity in the ARSACS population. A progression rate beyond the normal aging process was observed. These results provide fundamental insights regarding the disease prognosis that will help to better inform patients, develop specific rehabilitation programs, and improve trial readiness.
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Ataxia Cerebelar , Deficiência Intelectual , Atrofia Óptica , Ataxias Espinocerebelares , Humanos , Estudos Longitudinais , Ataxias Espinocerebelares/genética , Espasticidade Muscular , AtaxiaRESUMO
Mobility limitations, including a decrease in walking speed, are major issues for people with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Improving our understanding of factors influencing walking speed in ARSACS may inform the development of future interventions for gait rehabilitation and contribute to better clinical practices. The objective of the study was to identify the factors influencing the self-selected walking speed in adults with ARSACS. The dependent variable of this cross-sectional study was the self-selected speed and the factors (independent variables) were age, sex, balance, balance confidence, knee flexion and extension cocontraction indexes, lower limb coordination, passive range of motion of ankle dorsiflexion, knee and hip extension, and global spasticity. Multiple regression models were used to assess the relationships between walking speed and each factor individually. Six factors were significantly associated with walking speed and thus included in regression models. The models explained between 42.4 and 66.5% of the total variance of the self-selected walking speed. The factors that most influence self-selected walking speed are balance and lower limb coordination. In order of importance, the other factors that also significantly influence self-selected walking speed are ankle dorsiflexion range of motion, lower limb spasticity, knee extension range of motion, and confidence in balance. Balance and lower limb coordination should be targeted in rehabilitation interventions to maintain walking ability and functional independence as long as possible. The six factors identified should also be included in future studies to deepen our understanding of walking speed.
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Espasticidade Muscular , Velocidade de Caminhada , Humanos , Masculino , Feminino , Velocidade de Caminhada/fisiologia , Adulto , Estudos Transversais , Espasticidade Muscular/fisiopatologia , Espasticidade Muscular/reabilitação , Pessoa de Meia-Idade , Ataxias Espinocerebelares/fisiopatologia , Ataxias Espinocerebelares/reabilitação , Ataxias Espinocerebelares/congênito , Amplitude de Movimento Articular/fisiologia , Adulto Jovem , Equilíbrio Postural/fisiologia , Caminhada/fisiologiaRESUMO
The objective was to characterize the progression of sleep complaints in 115 dystrophy type 1 (DM1) patients who filled out a sleep questionnaire twice at a 9-year interval. Daytime napping (22.1% vs. 34.5%, p < 0.05), early awakenings (11.4% vs 21.1%, p < 0.05), nonrestorative sleep (39.5% vs 51.8%, p < 0.05), stimulant use (7.0% vs 19.3%, p < 0.01), breathing cessation (10.7% vs 23.2%, p < 0.01), and nighttime urination (42.5% vs 54.9%, p < 0.05) increased between Time 1 and Time 2. Sleep-related complaints are prominent and augment rapidly in DM1 patients. Physicians need to better identify and treat them to help alleviate the burden they impose on patients and their caregivers.
Évolution des troubles du sommeil dans la dystrophie myotonique de type 1 : une étude longitudinale de 9 ans.L'objectif était de caractériser l'évolution des plaintes liées au sommeil chez 115 patients atteints de dystrophie myotonique de type 1 (DM1) ayant rempli un questionnaire sur le sommeil à deux reprises à 9 ans d'intervalle. La prévalence des siestes (22,1 % vs 34,5 %, p < 0,05), des réveils matinaux précoces (11,4 % vs 21,1 %, p < 0,05), du sommeil non réparateur (39,5 % vs 51,8 %, p < 0,05), de la consommation de stimulants (7,0 % vs 19,3 %, p < 0,01), des arrêts respiratoires (10,7 % vs 23,2 %, p < 0,01) et des mictions nocturnes (42,5 % vs 54,9 %, p < 0,05) a augmenté entre le temps 1 et le temps 2. Les plaintes liées au sommeil sont fréquentes et augmentent rapidement dans la DM1. Les médecins doivent mieux les identifier et les traiter pour aider à alléger le fardeau qu'ils imposent aux patients et à leurs aidants.
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Distúrbios do Sono por Sonolência Excessiva , Distrofia Miotônica , Humanos , Distrofia Miotônica/complicações , Estudos Longitudinais , SonoRESUMO
The Scale for the Assessment and Rating of Ataxia (SARA) is a widely used scale for assessing the severity of ataxia in clinics, natural history studies, and treatment trials worldwide. However, no French translation with validated cross-cultural adaptation is available. This study aimed to translate and adapt the SARA into French. The translation process was conducted according to the ISPOR guidelines for the translation and cultural adaptation process for patient-reported outcomes. A total of five translators, an expert committee, and two physiotherapists took part in the process to assess and ensure comprehension and language equivalences of the final French version. A few misinterpretations were pointed out during the translation process and were changed accordingly by the translation team. The French version of the SARA is ready to be used in clinical and research settings with French-speaking populations living with ataxia.
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Ataxia Cerebelar , Comparação Transcultural , Humanos , Inquéritos e Questionários , Reprodutibilidade dos Testes , Psicometria , IdiomaRESUMO
INTRODUCTION/AIMS: Muscle weakness, and its association with mobility limitations, has received little study in oculopharyngeal muscular dystrophy (OPMD) using quantitative and standardized assessments. The objectives of this study were to (1) document upper and lower limb muscle strength, upper limb functions, fatigue, and mobility capacities; (2) compare them with reference values and across participant age groups; and (3) explore associations between muscle strength, fatigue, and mobility capacities among adults with OPMD. METHODS: Thirty-four participants were included in this cross-sectional study. The following variables were assessed: quantitative maximal isometric muscle strength, grip and pinch strength, fatigue, walking speed, walking endurance, sit-to-stand, and stair ascent and descent capacities. RESULTS: Muscle strength was lower for older than younger participants for five muscle groups (P < .05). Walking endurance, sit-to-stand, stairs (ascent and descent), and strength of hip flexion, grip, and pinch were below 80% of reference values in participants ≥56 y old (55.3%-78.2%). Moderate to strong correlations were found between muscle strength and mobility capacities (ρ = 0.42-0.80, P < .05), and between fatigue and either muscle strength or mobility capacities (ρ = 0.42-0.75, P < .05). DISCUSSION: This study highlights the impact of OPMD on strength, endurance, and functional capacity, among others, with patients being well below reference values even before the age of 65 y. In addition to helping health professionals to offer better clinical guidance, these results will improve clinical trial readiness. The next steps will be to assess the metrological properties of outcome measures and continue to document the disease progression rate.
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Distrofia Muscular Oculofaríngea , Adulto , Humanos , Estudos Transversais , Força Muscular/fisiologia , Caminhada/fisiologia , FadigaRESUMO
The Traumatic Grief Inventory Self-Report (TGI-SR), which aims to assess both Persistent Complex Bereavement Disorder and Prolonged Grief Disorder, has been validated in several languages. This study sought to validate the French-Canadian version. We conducted an online survey exploring the impact of the COVID-19 pandemic on grief. With data from 728 participants, the scale demonstrated high internal consistency, correlated significantly with three other scales known to measure similar concepts, and distinguished between groups known to be different. This study supports the use of the TGI-SR French-Canadian version by clinicians and researchers to assess complications of grief.
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Luto , COVID-19 , Humanos , Autorrelato , Transtorno do Luto Prolongado , Pandemias , Canadá , Pesar , IdiomaRESUMO
INTRODUCTION/AIMS: Myotonic dystrophy type 1 (DM1) is a neuromuscular disease affecting many systems and for which muscle weakness is one of the cardinal symptoms. People with DM1 also present with balance-related impairments and high fall risk. The aim of this study was to explore explanatory factors of dynamic balance impairment in the DM1 population. METHODS: A secondary analysis of data collected as part of a larger study was performed. The Mini Balance Evaluation System Test (Mini-BESTest) was used to assess dynamic balance. Age, sex, and CTG repeat length in blood were retrieved from medical records and research files. The maximal isometric muscle strength of five lower limb muscle groups (hip flexors and extensors, knee flexors and extensors, and ankle dorsiflexors) was quantitatively assessed as well as fatigue. Standard multiple regression analysis was used. RESULTS: Fifty-two individuals (31 men) aged between 24 and 81 years were included. The final model explains 65.9% of the balance score; ankle dorsiflexor muscle strength was the strongest explanatory factor, followed by CTG repeat length, age and fatigue to a lesser extent. DISCUSSION: Dynamic balance is impaired in people with DM1. Results of this study suggest that rehabilitation interventions aimed at improving strength of the ankle dorsiflexors and managing fatigue could help to improve dynamic balance in this specific population.
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Distrofia Miotônica , Adulto , Idoso , Idoso de 80 Anos ou mais , Fadiga , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Debilidade Muscular/etiologia , Músculo Esquelético , Distrofia Miotônica/complicações , Distrofia Miotônica/diagnóstico , Distrofia Miotônica/genética , Adulto JovemRESUMO
PURPOSE: Patient-reported outcomes (PRO) assessing dysphagia are an essential component of clinical trials to consider how patients feel and function in response to treatments. The selected PRO needs to be translated in several languages using a systematic process ensuring its validity and equivalence for use in multicenter clinical trials. The main objectives were to translate the SWAL-QOL and the Sydney Swallow Questionnaire (SSQ) into French Canadian (SWAL-QOL-FC and SSQ-FC) and to assess their appropriateness for patients with oculopharyngeal muscular dystrophy (OPMD). METHODS: A forward- and back-translation process was followed including independent mother-tongue translators followed by committee review. Known-groups validity was assessed by comparing scores of OPMD French-Canadian participants (n = 21) known to differ in dysphagia severity according to the 80-ml drinking test score. A Mann-Whitney test was used to compare the mean scores. Cognitive interviews were conducted later on to ensure a posteriori cultural equivalence among French-Canadian participants (n = 28). RESULTS: Evidences of adequate known-groups validity was shown for the SSQ-FC. Only two domains out of 10 of the SWAL-QOL-FC (burden and eating duration) showed adequate known-groups validity. In addition, the difference in the mean composite score was not significant. Several conceptual equivalence issues were found in both questionnaires as a result of the cognitive interviews. CONCLUSION: This study provided evidence that the SSQ-FC presents better validity than the SWAL-QOL-FC in a small sample size of OPMD participants. The findings of the cognitive interviews suggest the need to develop an OPMD-specific questionnaire to capture better the whole spectrum of disease severity.
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Transtornos de Deglutição , Distrofia Muscular Oculofaríngea , Canadá , Comparação Transcultural , Humanos , Idioma , Qualidade de Vida/psicologia , Inquéritos e QuestionáriosRESUMO
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.
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Distúrbios do Sono por Sonolência Excessiva , Distrofia Miotônica , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/etiologia , Fadiga/diagnóstico , Fadiga/etiologia , Humanos , Distrofia Miotônica/complicações , Distrofia Miotônica/diagnóstico , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Psychometric properties of the Teruel Orthorexia Scale (TOS) have been examined in several languages (Arabic, English, Portuguese, Spanish, and Turkish), but not in French. PURPOSE: The objective was to examine the psychometric properties of the TOS among a French-Canadian adult sample. METHODS: Participants were 296 French-speaking Canadian adults (M = 34.2 years, SD = 11.9, 85.1% women). They completed the TOS alongside with several other measures (e.g., alcoholic consumption, cigarette smoking, disturbed eating attitudes and behaviors, frequency of physical activities, intuitive eating, vegetarian diet, and negative affect). RESULTS: The results supported the a priori two-factor representation (orthorexia nervosa and healthy orthorexia) of the French version of the TOS and provided further support for the superiority of an exploratory structural equation modeling approach, relative to a confirmatory factor analytic approach. Furthermore, the results supported no differential item functioning as a function of respondents' characteristics (age, body mass index, diagnosis of eating disorders, frequency of physical activities, gender, and vegetarian diet). Latent mean differences were found in healthy orthorexia and orthorexia nervosa factors as a function of respondents' characteristics. Finally, significant correlations were found between TOS factors and convergent measures (alcohol consumption, cigarette smoking, disturbed eating attitudes and behaviors, intuitive eating, and negative affect). CONCLUSION: The present study confirmed that the French version of the TOS has satisfactory psychometric properties (i.e., factor validity and reliability, no differential item functioning, and convergent validity). LEVEL OF EVIDENCE: V, cross-sectional study.
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Transtornos da Alimentação e da Ingestão de Alimentos , Ortorexia Nervosa , Adulto , Humanos , Feminino , Masculino , Comportamentos Relacionados com a Saúde , Psicometria , Estudos Transversais , Reprodutibilidade dos Testes , Canadá , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Comportamento Alimentar , Inquéritos e QuestionáriosRESUMO
Myotonic dystrophy type 1 (DM1) is an autosomal dominant inherited disorder caused by expansion of a germline and somatically unstable CTG repeat in the DMPK gene. Previously, CTG repeat length at birth has been correlated to patient age at symptom onset. Attempts to correlate CTG repeat length with progressive DM1 phenotypes, such as muscle power, have proven difficult. To better correlate genotype with progressive phenotypes, we have measured CTG repeat tract length and screened for interrupting variant repeats in 192 study participants from a well-characterized Canadian cohort. We have assessed genotype-phenotype correlations with nine progressive measures of skeletal muscle power and respiratory function. We have built statistical models that include confounding factors such as sex, age, height and weight to further explain variation in muscle power. Our analysis reveals a strong correlation between DM1 genotype and respiratory function and skeletal muscle power, as part of a complex model that includes additional modulators such as sex, age, height, weight and the presence or absence of interrupting variant repeats. Distal skeletal muscle measurements, such as hand pinch and grip strength, show the strongest correlation with disease genotype. Detailed analysis of CTG repeat length, and incorporation of confounding factors, greatly improves the predictive ability of these models. They reveal a greater genetic influence on individual progressive phenotypes than on age at symptom onset and for clinical trials will help optimize stratification and explain patient variability. They will also help practitioners prioritize assessment of the muscular power measurements that correlate best with disease severity.
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Músculo Esquelético/fisiopatologia , Distrofia Miotônica/genética , Miotonina Proteína Quinase/genética , Expansão das Repetições de Trinucleotídeos , Alelos , Canadá , Estudos de Coortes , Feminino , Estudos de Associação Genética , Genótipo , Força da Mão/fisiologia , Humanos , Masculino , Modelos Estatísticos , Distrofia Miotônica/fisiopatologia , Fenótipo , Testes de Função RespiratóriaRESUMO
Purpose: To document the nutritional risk in adults with oculopharyngeal muscular dystrophy (OPMD) and its association with oropharyngeal dysphagia.Methods: In this cross-sectional study, 33 adults with molecular confirmation of OPMD between 50 and 75 years old were recruited from the registry of a university-affiliated neuromuscular clinic. Nutritional risk was assessed with the French version of Seniors in the Community: Risk Evaluation for Eating and Nutrition II (SCREEN II), whereas the severity of dysphagia was assessed using the French-Canadian version of the Sydney Swallow Questionnaire. Anthropometric measurements were performed with standardized procedures.Results: SCREEN II scores showed high nutritional risk for 81.8% of OPMD participants with 6 factors contributing to nutritional risk in at least 50% of the sample. Pearson's correlational analysis showed a significant moderate relationship between dysphagia and nutritional risk (r = -0.470; P = 0.006).Conclusion: To our knowledge, this study is the first to investigate the nutritional risk of adults with OPMD. Our results indicate that individuals with OPMD may be at high nutritional risk mostly associated with swallowing difficulty, in the absence of a low body mass index. The present study highlights the need for dietary counseling in OPMD.
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Transtornos de Deglutição , Distrofia Muscular Oculofaríngea , Adulto , Idoso , Canadá , Estudos Transversais , Transtornos de Deglutição/complicações , Humanos , Pessoa de Meia-Idade , Distrofia Muscular Oculofaríngea/complicações , Inquéritos e QuestionáriosRESUMO
CTG repeat expansions in DMPK cause myotonic dystrophy (DM1) with a continuum of severity and ages of onset. Congenital DM1 (CDM1), the most severe form, presents distinct clinical features, large expansions, and almost exclusive maternal transmission. The correlation between CDM1 and expansion size is not absolute, suggesting contributions of other factors. We determined CpG methylation flanking the CTG repeat in 79 blood samples from 20 CDM1-affected individuals; 21, 27, and 11 individuals with DM1 but not CDM1 (henceforth non-CDM1) with maternal, paternal, and unknown inheritance; and collections of maternally and paternally derived chorionic villus samples (7 CVSs) and human embryonic stem cells (4 hESCs). All but two CDM1-affected individuals showed high levels of methylation upstream and downstream of the repeat, greater than non-CDM1 individuals (p = 7.04958 × 10-12). Most non-CDM1 individuals were devoid of methylation, where one in six showed downstream methylation. Only two non-CDM1 individuals showed upstream methylation, and these were maternally derived childhood onset, suggesting a continuum of methylation with age of onset. Only maternally derived hESCs and CVSs showed upstream methylation. In contrast, paternally derived samples (27 blood samples, 3 CVSs, and 2 hESCs) never showed upstream methylation. CTG tract length did not strictly correlate with CDM1 or methylation. Thus, methylation patterns flanking the CTG repeat are stronger indicators of CDM1 than repeat size. Spermatogonia with upstream methylation may not survive due to methylation-induced reduced expression of the adjacent SIX5, thereby protecting DM1-affected fathers from having CDM1-affected children. Thus, DMPK methylation may account for the maternal bias for CDM1 transmission, larger maternal CTG expansions, age of onset, and clinical continuum, and may serve as a diagnostic indicator.
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Ilhas de CpG , Metilação de DNA , Distrofia Miotônica/genética , Miotonina Proteína Quinase/genética , Adolescente , Adulto , Sequência de Bases , Linhagem Celular , Criança , Feminino , Células-Tronco Embrionárias Humanas/química , Humanos , Modelos Lineares , Masculino , Linhagem , Gravidez , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Adulto JovemRESUMO
INTRODUCTION: In this study we aimed to document the prevalence and age of onset of motor impairments and other key symptoms in oculopharyngeal muscular dystrophy (OPMD). METHODS: Retrospective chart review of patients followed at the Saguenay Neuromuscular Clinic (Quebec, Canada). RESULTS: A total of 333 participants with the (GCN)13 mutation were included. Before the age of 75 years, 27% of them had walking limitations, 14% could not climb stairs independently, and 14% used a wheelchair for long distances or daily living. The median age of onset was 54 years for ptosis and dysphagia and 58 years for lower limb proximal weakness. Other frequent symptoms included fatigue, pharyngeal pooling of thickened secretions, and dysphonia. The median age at death was 77 years and the main cause was respiratory disease. DISCUSSION: This study provides important information to help anticipatory guidance for affected people and for the development of therapeutic trials in OPMD.
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Atividades Cotidianas , Blefaroptose/fisiopatologia , Transtornos de Deglutição/fisiopatologia , Disfonia/fisiopatologia , Fadiga/fisiopatologia , Limitação da Mobilidade , Debilidade Muscular/fisiopatologia , Distrofia Muscular Oculofaríngea/fisiopatologia , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Creatina Quinase/sangue , Progressão da Doença , Eletromiografia , Feminino , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Distrofia Muscular Oculofaríngea/sangue , Distrofia Muscular Oculofaríngea/genética , Proteína I de Ligação a Poli(A)/genética , Estudos Retrospectivos , Taxa de Sobrevida , Expansão das Repetições de Trinucleotídeos , Cadeiras de RodasRESUMO
INTRODUCTION: Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular disease that causes balance problems. The objective of this study was to assess the construct validity of the Mini-BESTest among adults with DM1. METHODS: Fifty-nine individuals with late-onset or adult phenotypes of DM1 were recruited. Participants performed the Mini-BESTest, 10-Meter Walk Test (10mWT), 6-Minute Walk Test (6MWT), and Timed Up & Go (TUG) and were questioned on their tendency to lose balance and whether they fell in the past month. RESULTS: Scores on the Mini-BESTest were significantly different between phenotypes and CTG repeat numbers (P < .02). Significant correlations were found with the 10mWT, 6MWT, and the TUG (r = 0.77-0.84; P < .001). A cutoff score of 21.5 was found to identify fallers with 90% posttest accuracy. DISCUSSION: The Mini-BESTest demonstrates evidence of construct validity when assessing balance in the DM1 population.
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Distrofia Miotônica/diagnóstico , Distrofia Miotônica/fisiopatologia , Equilíbrio Postural/fisiologia , Teste de Caminhada/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Teste de Caminhada/métodosRESUMO
INTRODUCTION: There is currently little evidence regarding oculopharyngeal muscular dystrophy (OPMD) disease burden reported by patients. In this study we aim to elicit direct patient input regarding OPMD disease burden. METHODS: We conducted semistructured interviews with 25 participants with genetically confirmed OPMD and a wide range of disease duration (15 ± 8 years). Using the Framework Technique, themes and categories were then extracted. RESULTS: Analyses revealed 7 themes (physical impact, mental impact, social impact, perception of progression, treatment perceptions, coping strategies, and access to disease information), encompassing 27 categories of OPMD disease burden. The most frequent categories were related to dysphagia, coping strategies for dysphagia, and impaired mobility. DISCUSSION: This study demonstrates the importance of considering, when providing clinical care, the broad range of coping strategies patients use to deal with OPMD symptoms, especially dysphagia, to properly assess limitations and monitor real disease progression.
Assuntos
Distrofia Muscular Oculofaríngea/fisiopatologia , Distrofia Muscular Oculofaríngea/psicologia , Acesso à Informação , Adaptação Psicológica , Adolescente , Adulto , Idoso , Atitude Frente a Saúde , Transtornos Dismórficos Corporais , Criança , Efeitos Psicossociais da Doença , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Distrofia Muscular Oculofaríngea/complicações , Distrofia Muscular Oculofaríngea/terapia , Dor/etiologia , Dor/fisiopatologia , Medidas de Resultados Relatados pelo Paciente , Angústia Psicológica , Pesquisa Qualitativa , Participação Social , Distúrbios da Voz/etiologia , Distúrbios da Voz/fisiopatologia , Desempenho Profissional , Adulto JovemRESUMO
INTRODUCTION: There is no patient-reported outcome (PRO) questionnaire specifically designed to assess oropharyngeal dysphagia in oculopharyngeal muscular dystrophy (OPMD). To select a suitable questionnaire, content validity of the existing questionnaires must be assessed. This study sought (1) to identify dysphagia-related symptoms in OPMD and (2) to assess content validity of currently available PRO for the assessment of dysphagia severity in OPMD. METHODS: A two-step literature review was conducted of dysphagia-related symptom identification and oropharyngeal dysphagia-related PRO. Symptoms were validated with an expert panel by using a Delphi survey. Content validity of PRO questionnaires was documented through content analysis. RESULTS: Ten PRO questionnaires were identified. None of the questionnaires cover the entire symptom spectrum in OPMD and thus lack content validity. DISCUSSION: The development and validation of a new PRO questionnaire to assess dysphagia in OPMD is required to establish the importance of symptomatic relief from new treatments. Muscle Nerve 59:445-450, 2019.