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STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 is mostly of central origin but it may coexist with sleep-related breathing disorders. However, there is no consensus on the sleep protocols to be used, assessments vary, and only a minority of patients are regularly tested or are on treatment for EDS. Our study presents data on self-reported and objective EDS in adult-onset myotonic dystrophy type 1. METHODS: Sixty-three patients with adult-onset DM1 were subjected to EDS-sleep assessments (polysomnography, Multiple Sleep Latency Test, Epworth Sleepiness Scale). Correlation coefficients were computed to assess the relationship between sleep and sleepiness test results, fatigue, and quality of life. RESULTS: 33% and 48% of patients had EDS based, respectively, on the Epworth Sleepiness Scale and the Multiple Sleep Latency Test, with a low concordance between these tests (k = 0.19). Thirteen patients (20%) displayed 2 or more sleep-onset rapid eye movement periods on Multiple Sleep Latency Test. Patients having EDS by Multiple Sleep Latency Test had a shorter disease duration (P < .05), higher total sleep time and sleep efficiency and lower wake after sleep onset on polysomnography. Patients with self-reported EDS reported significantly higher fatigue score compared with patients without EDS (P < .05). No other difference was found in demographic, clinical, and respiratory features. CONCLUSIONS: EDS test results are contradictory, making treatment options difficult. Combining quantitative tests and self-reported scales may facilitate physicians in planning EDS care with patients and families. CITATION: Sansone VA, Proserpio P, Mauro L, et al. Assessment of self-reported and objective daytime sleepiness in adult-onset myotonic dystrophy type 1. J Clin Sleep Med. 2021;17(12):2383–2391.

Respiratory insufficiency is one of the main causes of death in myotonic dystrophy type 1 (DM1). Although there is general consensus these patients have a restrictive ventilatory pattern, hypoventilation, chronic hypercapnia and sleep disturbances, the prevalence of respiratory disease and indication for and effects of non-invasive ventilation (NIV) need to be further explored.We aim to describe the respiratory function and the need for NIV at baseline and over time in a cohort of adult patients with DM1.One hundred and fifty-one adult patients with DM1 were subjected to arterial blood gas analysis, sitting and supine forced vital capacity (FVC), peak cough expiratory flow (PCEF), nocturnal oximetry, maximal inspiratory and expiratory pressures (MIP/PEP).On first assessment 84 of 151 had normal respiratory function (median age 38 years, median BMI 23.9, median disease duration: 11 years); 67 received an indication to use NIV (median age: 49 years, median BMI: 25,8, median disease duration: 14 years). After a median time of 3.85 years, 43 patients were lost to follow-up; 9 of 84 required NIV; only 17 of 67 with the new NIV prescription were adherent.We provide additional data on the natural history of respiratory function decline and treatment adherence in a relatively large cohort of well-characterized patients with DM1. A high proportion (28%) were lost to follow-up. A minority (11%) required NIV, and only 25% were treatment adherent, irrespective of specific demographics and respiratory features. Our results also confirm previous findings showing that age, disease duration and higher BMIs are predisposing factors for respiratory impairment.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the motor neuron, which selectively affects it both at central (first motor-neuron) and peripheral level (second motor-neuron). The disease shows up at a mean age of 56 years and the most affected are males. Although ALS may start as a bulbar or spinal disease, with the progression of the disease typically both become evident. Pharmacological approved treatments for ALS are still limited and include riluzole and edaravone which improve survival over time. Despite this, ALS leads to progressive muscle involvement and requires a complex multidisciplinary approach to manage increasing disability which goes beyond motor neurons. Sialorrhea is, amongst others, one of the most disabling symptoms in ALS. The complexity in managing saliva is due to a muscular spasticity and to a scarce palatino-lingual muscles control, rather than to an overproduction of saliva. These features could increase the risk of aspiration pneumonia and limit the use of noninvasive mechanical ventilation. We reviewed the treatment for sialorrhea in ALS patients that are available at this time, emphasizing pros and cons for each approach. Our purpose is to create a practical tool for the diagnosis, in order to facilitate the quantification and management of sialorrhea in everyday practice.

Nusinsersen is now available in Italy for all SMA types. We describe the experience with intrathecal treatment with nusinersen in 50 patients with SMA at the NEMO Center (NEuroMuscular Omniservice Clinical Center) in Milan, a neuromuscular patient-centered clinic hosted within Niguarda Hospital, a National Public General Hospital. Our results indicate that the pathway of care described outweighs the burden due to the repeated intrathecal injections. Irrespective of age and severity, the treatment is feasible, accessible, and replicable provided that there is a multidisciplinary team having experience and training in SMA.

Monitoring a patient in long-term non-invasive ventilation (LTNIV) requires the availability and the wide knowledge of tools such as nocturnal pulse oximetry, polysomnography/polygraphy (PSG/PG), capnography and arterial blood gas analysis (ABG). During the last few years, some manufacturers have incorporated in their ventilators special softwares that are able to detect, during non-invasive ventilation (NIV), respiratory parameters such as air leaks, residual apnoeic/hypopnoeic events and the patient’s daily compliance in the ventilator’s utilization. The clinician’s skills are then necessary for the cautious evaluation and interpretation of this data in order to improve the ventilator’s settings.

Objective: Respiratory insufficiency is a major complication of Duchenne muscular dystrophy (DMD).Its progression shows considerable interindividual variability, which has been less thoroughly characterized and understood than in skeletal muscle. We collected pulmonary function testing (PFT) data from a large retrospective cohort followed at Centers collaborating in the Italian DMD Network. Furthermore, we analyzed PFT associations with different DMD mutation types, and with genetic variants in SPP1, LTBP4, CD40, and ACTN3, known to modify skeletal muscle weakness in DMD. Genetic association findings were independently validated in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS). Methods and Results: Generalized estimating equation analysis of 1852 PFTs from 327 Italian DMD patients, over an average follow-up time of 4.5years, estimated that forced vital capacity (FVC) declined yearly by −4.2%, forced expiratory volume in 1sec by −5.0%, and peak expiratory flow (PEF) by −2.9%. Glucocorticoid (GC) treatment was associated with higher values of all PFT measures (approximately+15% across disease stages). Mutations situated 3’ of DMD intron 44, thus predicted to alter the expression of short dystrophin isoforms, were associated with lower (approximately −6%) PFT values, a finding independently validated in the CINRG-DNHS. Deletions amenable to skipping of exon 51 and 53 were independently associated with worse PFT outcomes. A meta-analysis of the two cohorts identified detrimental effects of SPP1 rs28357094 and CD40 rs1883832 minor alleles on both FVC and PEF. Interpretation: These findings support GC efficacy in delaying respiratory insufficiency, and will be useful for the design and interpretation of clinical trials focused on respiratory endpoints in DMD.

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative motor neuron disease that can lead to rapid deterioration of respiratory function. Noninvasive ventilation (NIV) has been shown to slow the progression of respiratory deterioration, improving patient survival and quality of life. In recent years the scientific debate has focused on some items such as the early start of NIV, the NIV modalities, and the settings and monitoring of the patient on NIV. In this work the most interesting studies published in the last 2 years have been reviewed to summarize the key points.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the motor neuron, which selectively affects it both at central (first motor-neuron) and peripheral level (second motor-neuron). The disease shows up at a mean age of 56 years and the most affected are males. Although ALS may start as a bulbar or spinal disease, with the progression of the disease typically both become evident. Pharmacological approved treatments for ALS are still limited and include riluzole and edaravone which improve survival over time. Despite this, ALS leads to progressive muscle involvement and requires a complex multidisciplinary approach to manage increasing disability which goes beyond motor neurons. Sialorrhea is, amongst others, one of the most disabling symptoms in ALS. The complexity in managing saliva is due to a muscular spasticity and to a scarce palatino-lingual muscles control, rather than to an overproduction of saliva. These features could increase the risk of aspiration pneumonia and limit the use of noninvasive mechanical ventilation. We reviewed the treatment for sialorrhea in ALS patients that are available at this time, emphasizing pros and cons for each approach. Our purpose is to create a practical tool for the diagnosis, in order to facilitate the quantification and management of sialorrhea in everyday practice.

Noninvasive ventilation (NIV) is an increasingly used method of respiratory support. The use of NIV is expanding over the time and if properly applied, it can save patients' lives and improve long-term prognosis. However, both knowledge and skills of its proper use as life support are paramount. This systematic review aimed to assess the importance of NIV education and training. Literature search was conducted (MEDLINE: 1990 to June, 2018) to identify randomized controlled studies and systematic reviews with the results analyzed by a team of experts across the world through e-mail based communications. Clinical trials examining the impact of education and training in NIV as the primary objective was not found. A few studies with indirect evidence, a simulation-based training study, and narrative reviews were identified. Currently organized training in NIV is implemented only in a few developed countries. Due to a lack of high-grade experimental evidence, an international consensus on NIV education and training based on opinions from 64 experts across the twenty-one different countries of the world was formulated. Education and training have the potential to increase knowledge and skills of the clinical staff who deliver medical care using NIV. There is a genuine need to develop structured, organized NIV education and training programs, especially for the developing countries. info:eu-repo/semantics/publishedVersion

Objective To evaluate the effects of nusinersen on respiratory function of patients with type 1 spinal muscular atrophy. Study design Observational, longitudinal cohort study. We collected respiratory data from 118 children with type 1 spinal muscular atrophy and differing pulmonary requirements and conducted a semistructured qualitative interview among a subsample of caregivers at baseline, 6 months, and 10 months after the first nusinersen treatment. Patients were stratified according to ventilation modalities and age at study entry. Results Most patients in our cohort remained stable (84/109 = 77%). More than 80% of the children treated before age 2 years survived, in contrast to the lower survival reported in natural history studies, and did so without tracheostomy or noninvasive ventilation (NIV) ≥16 hours. In those less than 2 years old, only 3 patients shifted from NIV ≤10 hours to NIV >10 hours, and the other 3 reduced the hours of NIV required. Most of the older patients remained stable; this included not only those on tracheostomy or NIV >10 hours but also 75% of those on NIV ≤10 hours. Conclusions Our results suggest that nusinersen may produce some improvement in the progression of respiratory impairment, both in terms of survival and need for respiratory support ≥16 hours, especially before the age of 2 years.

BACKGROUND: Until recently, it has been considered essential to maintain the use of a double-limb circuit in patients with amyotrophic lateral sclerosis (ALS) to avoid rebreathing expired air during invasive mechanical ventilation. Currently, life-sustaining home ventilators can work with a single, lighter circuit that is easier to manage. Our aim was to evaluate the effectiveness and safety of a single-limb circuit with intentional leaks (passive circuit) in comparison with a circuit with an expiratory valve (active circuit), in subjects with ALS who use invasive home ventilation. METHODS: We conducted a retrospective single-center study. The enrolled subjects were divided into 2 groups according to the type of exhalation port. The aim of the study was to compare arterial blood gases; nocturnal oxygen saturation recordings; and the occurrence of adverse events, both clinical and technical events. In addition, we compared the rate of mortality and unplanned hospital admissions that occurred within a year after discharge from the hospital. RESULTS: Forty-three subjects were included in our study: 23 who used a passive circuit and 20 who used an active circuit. No significant difference in nocturnal and diurnal gas exchanges was detected. The incidence of adverse events was significantly higher in the active circuit group (85% in active circuit vs 30% in passive circuit, P CONCLUSIONS: The passive circuit was shown to be as effective and safe as the active circuit during home invasive ventilation in the subjects with amyotrophic lateral sclerosis. A future randomized controlled study is necessary to confirm these results and to extend indications to other pathologies.

This is a unique state of the art review written by a group of 21 international recognized experts in the field that gathered during a meeting organized by the European Neuromuscular Centre (ENMC) in Naarden, March 2017. It systematically reports the entire evidence base for airway clearance techniques (ACTs) in both adults and children with neuromuscular disorders (NMD). We not only report randomised controlled trials, which in other systematic reviews conclude that there is a lack of evidence base to give an opinion, but also include case series and retrospective reviews of practice. For this review, we have classified ACTs as either proximal (cough augmentation) or peripheral (secretion mobilization). The review presents descriptions; standard definitions; the supporting evidence for and limitations of proximal and peripheral ACTs that are used in patients with NMD; as well as providing recommendations for objective measurements of efficacy, specifically for proximal ACTs. This state of the art review also highlights how ACTs may be adapted or modified for specific contexts (e.g. in people with bulbar insufficiency; children and infants) and recommends when and how each technique should be applied.

ObjectiveTo report cross-sectional clinical findings in a large cohort of patients affected by type 1 spinal muscular atrophy.MethodsWe included 122 patients, of age ranging between 3 months and 22 years, 1 month. More than 70% (85/122) were older than 2 years and 25% (31/122) older than 10 years. Patients were classified according to the severity of phenotype and to the number of SMN2 copies.ResultsPatients with the more common and the most severe phenotype older than 2 years were, with few exceptions, on noninvasive ventilation and, with increasing age, more often had tracheostomy or >16-hour ventilation and a gastrostomy inserted. In contrast, 25 of the 28 patients with the mildest phenotype older than 2 years had no need for tracheostomy or other ventilatory or nutritional support. In patients older than 2 years, the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores were generally lower compared to those found in younger patients and showed distinct levels of functional abilities according to the severity of the phenotype. Similar findings were also observed on the Hammersmith Infant Neurological Examination.ConclusionsOur findings confirm that, after the age of 2 years, patients with type 1 spinal muscular atrophy generally survive only if they have gastrostomy and tracheostomy or noninvasive ventilation >16 hours and have low scores on the functional scales. More variability, however, can be expected in those with the mildest phenotype, who achieve head control. These data provide important baseline information at the time treatments are becoming available.

Objective Amyotrophic lateral sclerosis (ALS) patients tend to develop progressive respiratory muscle weakness, leading to ventilatory failure and ineffective cough, principal causes of morbidity and mortality. Since patients are usually unaware of these symptoms, these are generally not noticed until the advanced stages and are associated with poor prognosis. The monitoring of respiratory function on a regular basis is therefore of great importance. Despite the availability of several pulmonary function tests, none of them was found to be the best indicator of the disease progression throughout the course of this condition. The main aim of our work was to evaluate the prognostic value of these respiratory measures evaluated in a brief period of observation and their correlation with motor functional impairments in an ALS cohort. Patients and Methods Patients with ALS who had respiratory assessments performed and functional motor scales administered at baseline and six months later were included. All patients were assessed with forced vital capacity, both in seated and supine position (FVC; sFVC), peak expiratory flow (PEF), peak expiratory cough flow (PCEF), the revised ALS functional rating scale (ALSFRS-R), at baseline and after six months, and their disease progression rate (ΔFS) was obtained. Results We included 73 patients with probable or definite ALS according to El-Escorial revised Criteria. At baseline, PCEF and PEF significantly correlated with ALSFRS-R total, bulbar and spinal subscores and ΔFS, while FVC% significantly correlated with ΔFS. After 6 months all the respiratory parameters significantly correlated with ALSFRS-R and all its subscores. Longitudinally, FVC%, sFVC% and PCEF significantly correlated with ΔFS and some of ALSFRS-R subscores. As concerns the survival analysis, monthly declines of FVC% and sFVC%, significantly correlated with the survival. The worse prognosis in terms of survival was finally found in those whose FVC% and sFVC% dropped below their respective cut-offs. Conclusion Throughout the course of ALS disease, the monitoring of several respiratory markers, namely FVC, sFVC, PEF and PCEF, plays a critical role in predicting the prognosis of these subjects, both in terms of survival and functional ability. The implementation of monthly cut-offs in the evaluation of FVC and sFVC may allow a faster recognition of those patients with worse prognosis and therefore an optimized tailored clinical care, as well as a better stratification in clinical trials.

OBJETIVO: Descrever as características dos pacientes com pneumonia associada a influenza A (H1N1) tratados em dois hospitais na região da Ligúria, Itália, e descrever seu tratamento e desfechos. MÉTODOS: Estudo prospectivo observacional que incluiu todos os pacientes com mais de 16 anos de idade e com diagnóstico confirmado de influenza A (H1N1) admitidos no Hospital Villa Scassi, em Gênova, ou no Hospital Geral de Sestri Levante, em Sestri Levante, Itália, entre setembro de 2009 e janeiro de 2010. O desfecho primário foi mortalidade em até 60 dias do diagnóstico, e os desfechos secundários foram necessidade de ventilação mecânica e tempo de hospitalização. RESULTADOS: Durante o período do estudo, dos 40 pacientes com diagnóstico confirmado de influenza A (H1N1), 27 apresentaram pneumonia. A média de idade dos 27 pacientes foi de 42,8 ± 14,8 anos, e o tempo médio de hospitalização foi de 11,6 ± 8,2 dias. Dos 27 pacientes, 20 tiveram insuficiência respiratória, 4 necessitaram de ventilação mecânica invasiva e 5, de ventilação mecânica não invasiva. Somente 1 paciente com várias comorbidades teve falência múltipla de órgãos e faleceu. CONCLUSÕES: Embora a influenza A (H1N1) tenha sido mais branda e com menor incidência de mortalidade na Itália do que em outros países, 9 de nossos pacientes (33%) tiveram evolução rápida para falência respiratória e necessitaram de ventilação mecânica. OBJECTIVE: To describe the characteristics of patients with influenza A (H1N1)-associated pneumonia treated at two hospitals in the region of Liguria, Italy, as well as to describe their treatment and outcomes. METHODS: This was a prospective observational study including all patients older than 16 years of age with a confirmed diagnosis of influenza A (H1N1) who were admitted to Villa Scassi Hospital, in the city of Genoa, Italy, or to the Sestri Levante General Hospital, in the city of Sestri Levante, Italy, between September of 2009 and January of 2010. The primary outcome measure was mortality within 60 days after diagnosis. Secondary outcome measures were the need for mechanical ventilation and the length of hospital stay. RESULTS: Of the 40 patients with a confirmed diagnosis of influenza A (H1N1), 27 presented pneumonia during the study period. The mean age of the 27 patients was 42.8 ± 14.8 years, and the mean length of hospital stay was 11.6 ± 8.2 days. Of the 27 patients, 20 had respiratory failure, 4 underwent invasive mechanical ventilation, and 5 underwent noninvasive ventilation. One patient had comorbidities, developed multiple organ failure, and died. CONCLUSIONS: During the influenza A (H1N1) pandemic, the associated mortality rate was lower in Italy than in other countries, and cases reported in the country typically had a milder course than did those reported elsewhere. Nevertheless, 9 of our cases (33%) rapidly evolved to respiratory failure, requiring mechanical ventilation.

To describe the characteristics of patients with influenza A (H1N1)-associated pneumonia treated at two hospitals in the region of Liguria, Italy, as well as to describe their treatment and outcomes.This was a prospective observational study including all patients older than 16 years of age with a confirmed diagnosis of influenza A (H1N1) who were admitted to Villa Scassi Hospital, in the city of Genoa, Italy, or to the Sestri Levante General Hospital, in the city of Sestri Levante, Italy, between September of 2009 and January of 2010. The primary outcome measure was mortality within 60 days after diagnosis. Secondary outcome measures were the need for mechanical ventilation and the length of hospital stay.Of the 40 patients with a confirmed diagnosis of influenza A (H1N1), 27 presented pneumonia during the study period. The mean age of the 27 patients was 42.8 ± 14.8 years, and the mean length of hospital stay was 11.6 ± 8.2 days. Of the 27 patients, 20 had respiratory failure, 4 underwent invasive mechanical ventilation, and 5 underwent noninvasive ventilation. One patient had comorbidities, developed multiple organ failure, and died.During the influenza A (H1N1) pandemic, the associated mortality rate was lower in Italy than in other countries, and cases reported in the country typically had a milder course than did those reported elsewhere. Nevertheless, 9 of our cases (33%) rapidly evolved to respiratory failure, requiring mechanical ventilation.