Adults with neuromuscular diseases like spinal muscular atrophy or Duchenne muscular dystrophy require full-time use of a wheelchair (WC) and perform all activities of daily living in a sitting ...position. Optimal configuration of the WC and seating system is essential to maintain the health and quality of life of users. However, few recommendations for configuration exist. The aim of this study was to identify and select 10 WC seating criteria that ensure an optimal sitting posture for health and quality of life. A four round Delphi method was used to collect the opinions of WC users and health professionals (HP), separately. First, the HP were asked if they believed that different criteria would apply to each disease. Then the HP and SMA II and DMD WC user experts responded to electronic surveys in 4 rounds. Overall, 74 experts took part: 31 HP, 21 WC users with SMA II and 22 WC users with DMD. In total, 52% of HP believed that different criteria would apply to each disease. Ten criteria were identified by the HP for SMA II and 10 for DMD. Of the 40 criteria selected, 30 (75%) were common to each panel. Six topics were similar across panels: comfort, access to the joystick, prevention of pain, stability, pressure management and power seat functions. However, power seat functions did not reach consensus between HP and WC users (30-33% of agreement for HP and 93-100% for the WC user panels, p < 0.001). Adults with SMA II and DMD had similar WC seating needs. Therefore, the same recommendations can be applied to these groups. Further research is necessary to understand the impact of cost on the prescription of power seat functions by health professionals.
SMA type 1 is a severe neurodegenerative disorder that, in the absence of curative treatment, leads to death before 1 year of age without ventilatory support. Three innovative therapies are available ...to increase life expectancy.
(i) To increase knowledge about parents' experiences with their decision to have opted for an innovative therapy; (ii) to assess the middle-term psychological consequences in the parents' lives.
We used an in-depth interview; a self-administrated questionnaire and self-report scales (BDI-II, STAI-Y, PSI-SF, SOC-13, PBA, DAS 16 and FICD). We compared parents hesitant before the decision to parents who were not-hesitant and the group of parents whose child was treated with gene therapy (GT) to parents whose child received another innovative therapy.
We included
= 18 parents of 13 children. Parent's mean age was 34.7 (±5.2), child's average age was 44.3 months (±38.0). Retrospectively, most parents felt involved by doctors in decision-making on treatment, they felt their point of view was considered and were satisfied with the effects of the treatment. The group of parents "non-hesitant" was more depressed (
< 0.001), more anxious (
= 0.022) and had higher parental stress (
= 0.026) than the group of "hesitant" parents; the group of "GT-treated" parents was more depressed (
= 0.036) than the group of parents with "other therapy". Qualitative data highlights revealed: the need to save the child's life at all costs; the fear of coping with end of life and palliative care, the high value of perceived physician confidence in the treatment, the hope that the child will acquire autonomy or be cured. At the time of the decision, no parents felt they fully understood all of the issues regarding therapy and the disease.
Hesitating before making a decision did not predispose parents to depression and anxiety. The narratives suggest that the parents faced a dilemma regarding their child's health in an urgent context. The decision was not final, and parents will continue to think about it throughout the care process.
Sleep-disordered breathing (SDB) is common in patients with neuromuscular diseases (NMD). Focusing on hypercapnia may lead to the neglect of other SDB such as obstructive and/or central sleep apnea ...syndrome (SAS). Our objectives were to assess the risk of inappropriate SDB management according to different screening strategies and to evaluate the prevalence and determinants of isolated and overlapping sleep apnea in patients with slowly progressive NMD.
This monocentric, cross-sectional, retrospective study analyzed medical records of adult NMD patients referred to a sleep department. Diagnostic strategies, including respiratory polygraphy (RP), nocturnal transcutaneous capnography (tcCO2), and blood gases (BG), were assessed for their performance in diagnosing SDB. Demographics and pulmonary function test results were compared between patients with or without SDB to identify predictors.
Among the 149 patients who underwent a full diagnostic panel (RP + tcCO2 + BG), 109 were diagnosed with SDB. Of these, 33% had isolated SAS, and central apneas were predominant. Using single diagnostic strategies would lead to inappropriate SDB management in two thirds of patients. A combination of 2 diagnostic tools resulted respectively in 21.1, 22.9 and 42.2 % of inappropriate SDB management for RP + tcCO2, RP + BG and tcCO2 + BG.
The significant prevalence of sleep apnea syndrome in patients with slowly progressive NMD highlights the need for increased awareness among clinicians. Improved diagnostics involve a systematic approach addressing both sleep apnea and diurnal and nocturnal alveolar hypoventilation to avoid inappropriate management and limit the consequences of SDB.
•In patients with NMD, focusing on hypercapnia may lead to neglect other SDB.•24% of slowly progressive NMD patients have isolated sleep apnea.•A single diagnostic strategy led to inappropriate management in two-thirds of patients.•This highlights the need for systematic diagnosis approach to improve management.
Objective
This study was undertaken to determine whether a low residual quantity of dystrophin protein is associated with delayed clinical milestones in patients with DMD mutations.
Methods
We ...performed a retrospective multicentric cohort study by using molecular and clinical data from patients with DMD mutations registered in the Universal Mutation Database–DMD France database. Patients with intronic, splice site, or nonsense DMD mutations, with available muscle biopsy Western blot data, were included irrespective of whether they presented with severe Duchenne muscular dystrophy (DMD) or milder Becker muscular dystrophy (BMD). Patients were separated into 3 groups based on dystrophin protein levels. Clinical outcomes were ages at appearance of first symptoms; loss of ambulation; fall in vital capacity and left ventricular ejection fraction; interventions such as spinal fusion, tracheostomy, and noninvasive ventilation; and death.
Results
Of 3,880 patients with DMD mutations, 90 with mutations of interest were included. Forty‐two patients expressed no dystrophin (group A), and 31 of 42 (74%) developed DMD. Thirty‐four patients had dystrophin quantities < 5% (group B), and 21 of 34 (61%) developed BMD. Fourteen patients had dystrophin quantities ≥ 5% (group C), and all but 4 who lost ambulation beyond 24 years of age were ambulant. Dystrophin quantities of <5%, as low as <0.5%, were associated with milder phenotype for most of the evaluated clinical outcomes, including age at loss of ambulation (p < 0.001).
Interpretation
Very low residual dystrophin protein quantity can cause a shift in disease phenotype from DMD toward BMD. ANN NEUROL 2021;89:280–292
•Most patients with SMA in Europe do not have access to the approved treatment.•Stabilization following treatment is considered progress.•Traditional SMA type classifications often do not reflect ...disease severity.•Patients want access to alternative treatments and clinical trials.•The active SMA community should be included in all stages of drug development.
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.
Cardiac Outcomes in Adults With Mitochondrial Diseases Savvatis, Konstantinos; Vissing, Christoffer Rasmus; Klouvi, Lori ...
Journal of the American College of Cardiology,
10/2022, Letnik:
80, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE).
We developed prediction models to estimate the risk of HF and arrhythmic ...MACE in this population.
We determined the incidence and searched for predictors of HF and arrhythmic MACE using Cox regression in 600 adult patients from a multicenter registry with genetically confirmed mitochondrial diseases.
Over a median follow-up time of 6.67 years, 29 patients (4.9%) reached the HF endpoint, including 19 hospitalizations for nonterminal HF, 2 cardiac transplantations, and 8 deaths from HF. Thirty others (5.1%) reached the arrhythmic MACE, including 21 with third-degree or type II second-degree atrioventricular blocks, 4 with sinus node dysfunction, and 5 sudden cardiac deaths. Predictors of HF were the m.3243A>G variant (HR: 4.3; 95% CI: 1.8-10.1), conduction defects (HR: 3.0; 95% CI: 1.3-6.9), left ventricular (LV) hypertrophy (HR: 2.6; 95% CI: 1.1-5.8), LV ejection fraction <50% (HR: 10.2; 95% CI: 4.6-22.3), and premature ventricular beats (HR: 4.1; 95% CI: 1.7-9.9). Independent predictors for arrhythmia were single, large-scale mtDNA deletions (HR: 4.3; 95% CI: 1.7-10.4), conduction defects (HR: 6.8; 95% CI: 3.0-15.4), and LV ejection fraction <50% (HR: 2.7; 95% CI: 1.1-7.1). C-indexes of the Cox regression models were 0.91 (95% CI: 0.88-0.95) and 0.80 (95% CI: 0.70-0.90) for the HF and arrhythmic MACE, respectively.
We developed the first prediction models for HF and arrhythmic MACE in patients with mitochondrial diseases using genetic variant type and simple cardiac assessments.
The prevalence of arterial hypertension in mitochondrial diseases remains unknown. Between January 2000 and May 2014, we retrospectively included patients with genetically proven mitochondrial ...diseases. We recorded clinical, genetic and cardiac exploration data, including the measure of arterial pressure. Among the 260 patients included in the study (mean age = 44 ± 15 years, women = 158), 108 (41.5%) presented with arterial hypertension. The prevalence of hypertension by sex and age was higher than that observed in the general population for all groups. The prevalence of hypertension was significantly higher in patients with MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke‐like episodes) mutations (66%) and MERRF (myoclonus, epilepsy, ataxia with ragged ref fibres) mutations (61%). In patients with MELAS mutation, the presence of hypertension was significantly associated with age and mutation rate in the blood (odds ratio = 1.12; P = .02) in multivariate analysis. The prevalence of hypertension was more important in patients having a mitochondrial disease. The increased risk was more important in patient with MELAS or MERRF and depended on the rate of heteroplasmy.
The life expectancy of individuals with Duchenne muscular dystrophy has improved considerably with the use of mechanical ventilation to manage respiratory insufficiency. The choice between continuous ...noninvasive ventilation (NIV) and invasive ventilation is guided both by local logistical considerations and by clinical considerations, but the choice depends largely on patient preference. It is important to know the effects of ventilatory dependence and the method used (ie, continuous NIV or invasive ventilation) on subjects' quality of life.
This was a cross-sectional prospective survey of 192 subjects with Duchenne muscular dystrophy using mechanical ventilation in France. Subjects were grouped and compared according to dependence on mechanical ventilation and the ventilation methods used.
Regardless of the mechanical ventilation method, subjects with gastrostomy tubes reported more frequent emergency consultations for digestive problems (22.5% vs 4.6%,
= .001). Subjects with invasive ventilation reported more insomnia than those with continuous NIV (23.8% vs 8.5%,
= .04). The latter reported more ineffective cough than the invasive ventilation group (72.3% vs 49.2%,
= .02). Overall, the subjects in our sample were satisfied with their medical care, regardless of dependence level or ventilation type. More specifically, 86.1% of subjects with intermittent NIV and 83.6% of ventilator-dependent subjects were satisfied.
Continuous and invasive mechanical ventilation did not affect the perception of quality of life for our subjects with Duchenne muscular dystrophy, apart from more insomnia, which can be explained by the fact that they required frequent repositioning in bed. Different pressure-relief mattresses should be tested and compared to prevent the development of pressure ulcers, which may improve the sleep patterns of these patients.
Les informations sur les maladies rares sont souvent de compréhension complexe et d’accès difficile. Un accompagnement est souvent nécessaire. Des services d’assistance du réseau européen ENRDHL
...(European Network ofRare Disease Help Lines)
travaillent ensemble à travers l’Europe pour répondre aux demandes de renseignements de tout public, incluant les patients et leurs proches, ainsi que les parties prenantes. Dans cet article, nous rapportons des données spécifiques aux maladies neuromusculaires sur la période 2012-2016, durant laquelle l’AFM-Téléthon a participé à l’enquête annuelle sur un mois donné de ce réseau coordonné par Eurordis.
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