Development of prediction models based on respiratory assessments to determine the need for non-invasive ventilation in patients with myotonic dystrophy type 1.

INTRODUCTION: Myotonic dystrophy type 1 is a slowly progressive, multisystem, autosomal dominant disorder, in which the impairments of respiratory systems represent one of the main causes of death. OBJECTIVE: The aim of our study is to develop prediction models to identify the most appropriate test(s) providing indication for NIV. METHODS: DM1 patients attending the NEMO Clinical Center (Milan) between January 2008 and July 2020, who had been subjected to a complete battery of respiratory tests, were retrospectively recruited. Demographic, clinical, and anthropometric characteristics were collected, as well as arterial blood gas (ABG) analysis, spirometry, respiratory muscle strength, cough efficacy, and nocturnal oximetry as respiratory assessments. Patients were stratified in those requiring NIV and those with normal respiratory function. RESULTS: Out of 151 DM1 patients (median age: 44 years [35.00-53.00]; male/female ratio: 0.80 (67/84)), 76 had an indication for NIV initiation (50.33%). ABG, spirometry, and nocturnal oximetry prediction models resulted in an excellent discriminatory ability in distinguishing patients who needed NIV from those who did not (AUC of 0.818, 0.808, and 0.935, respectively). An easy-to-use calculator was developed to automatically determine a score of NIV necessity based on the prediction equations generated from each aforementioned prediction model. CONCLUSIONS: The proposed prediction models may help to identify which patients are at a higher risk of requiring ventilator support and therefore help in defining individual management plans and criteria for specific interventions early in the disease course.

Consensus-Based Care Recommendations for Pulmonologists Treating Adults with Myotonic Dystrophy Type 1.

PURPOSE OF REVIEW: Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects approximately 1 in 2,500 individuals globally [Ashizawa et al.: Neurol Clin Pract 2018;8(6):507-20]. In patients with DM1, respiratory muscle weakness frequently evolves, leading to respiratory failure as the main cause of death in this patient population, followed by cardiac complications [de Die-Smulders et al.: Brain 1998;121(Pt 8):1557-63], [Mathieu et al.: Neurology 1999;52(8):1658-62], [Groh et al.: Muscle Nerve 2011;43(5):648-51]. This paper provides a more detailed outline on the diagnostic and management protocols, which can guide pulmonologists who may not have experience with DM1 or who are not part of a neuromuscular multidisciplinary clinic. A group of neuromuscular experts in DM1 including pulmonologists, respiratory physiotherapists and sleep specialists discussed respiratory testing and management at baseline and during follow-up visits, based on their clinical experience with patients with DM1. The details are presented in this report. RECENT FINDINGS: Myotonic recruited 66 international clinicians experienced in the treatment of people living with DM1 to develop and publish consensus-based care recommendations targeting all body systems affected by this disease [Ashizawa et al.: Neurol Clin Pract. 2018;8(6):507-20]. Myotonic then worked with 12 international respiratory therapists, pulmonologists and neurologists with long-standing experience in DM respiratory care to develop consensus-based care recommendations for pulmonologists using a methodology called the Single Text Procedure. This process generated a 7-page document that provides detailed respiratory care recommendations for the management of patients living with DM1. This consensus is completely based on expert opinion and not backed up by empirical evidence due to limited clinical care data available for respiratory care management in DM patients. Nevertheless, we believe it is of relevance for professionals treating adults with myotonic dystrophy because it addresses practical issues related to respiratory management and care, which have been adapted to meet the specific issues in patients with DM1. SUMMARY: The resulting recommendations are intended to improve respiratory care for the most vulnerable of DM1 patients and lower the risk of untoward respiratory complications and mortality by providing pulmonologist who are less experienced with DM1 with practical indications on which tests and when to perform them, adapting the general respiratory knowledge to specific issues related to this multiorgan disease.

Assessment of Respiratory Function and Need for Noninvasive Ventilation in a Cohort of Patients with Myotonic Dystrophy Type 1 Followed at One Single Expert Center.

Introduction: Respiratory insufficiency is one of the main causes of death in myotonic dystrophy type 1 (DM1). Although there is general consensus that these patients have a restrictive ventilatory pattern, hypoventilation, chronic hypercapnia, and sleep disturbances, the prevalence of respiratory disease and indication for the effects of noninvasive ventilation (NIV) need to be further explored. Objectives: To describe respiratory function and need for NIV at baseline and over time in a cohort of adult patients with DM1. Methods: A total of 151 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, and maximal inspiratory pressure and expiratory pressure (MIP/PEP). Results: On first assessment, 84 of 151 had normal respiratory function (median age: 38 years, median BMI: 23.9, and median disease duration: 11 years); 67 received an indication to use NIV (median age: 49 years, median BMI: 25,8, and 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. Conclusions: 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%) was 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.

Assessment of self-reported and objective daytime sleepiness in adult-onset myotonic dystrophy type 1.

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.

Screening for early symptoms of respiratory involvement in myotonic dystrophy type 1 using the Respicheck questionnaire.

Symptoms of respiratory involvement are frequently present but overlooked by patients with Myotonic Dystrophy type 1 (DM1). A respiratory symptom checklist was designed to test whether a DM-specifically designed checklist to detect symptoms of respiratory involvement (The Respicheck Questionnaire) could help patients be more aware of their respiratory problems, if any, and help clinicians in identifying potential candidates for intervention. The Respicheck questionnaire was administered to 58 consecutive adult-onset patients with genetically determined DM1 who did not complain of respiratory involvement per history at enrollment. Based on respiratory function test results patients were divided into 3 groups: A, (n = 17) having no signs of respiratory involvement; B (n = 13), patients having borderline results on respiratory assessments and having no need for respiratory intervention; C, (n = 28) patients having respiratory impairment requiring intervention. Respiratory test results and Respicheck scores were analyzed. Respicheck total score and subscales correlated positively with global respiratory impairment. Respicheck appears to be able to discriminate between patients having a higher level of respiratory dysfunction from those having a lower risk of respiratory involvement. This might allow to better target efforts and resources in respiratory management in DM1.

Passive Versus Active Circuit During Invasive Mechanical Ventilation in Subjects With Amyotrophic Lateral Sclerosis.

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 < .001). However, by splitting the adverse events into 2 categories, clinical and technical, the technical events were significantly more frequent in the active circuit group. None of these events led to hospital admission or death. 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.