Sleep disordered breathing: Assessment and therapy in the age of emerging neuromuscular therapies

Abstract

The term neuromuscular disease (NMD) encompasses a large variety of disorders that result in abnormal muscle function. Although it may be conventional to relate the use of this term to the most common muscular diseases (Duchenne muscular dystrophy [DMD], spinal muscular atrophy [SMA], and amyotrophic lateral sclerosis, etc), it is important to extend the term to pathologies manifested by severe neurologic (brain and spinal cord) malformations and injuries. In many of these scenarios, there are common mechanisms that contribute to sleep disordered breathing (SDB) and respiratory insufficiency although comorbidities may be somewhat different. Advances in the understanding of these diseases and their natural history, and increasing availability of mechanical ventilation to these patients have improved survival. The development of novel genetic and molecular therapies (as in the cases of DMD, SMA, and X‐linked myotubular myopathy) provides an opportunity to use SDB as a reasonable outcome measure while also allowing the use of polysomnography as a validation tool in the assessments of effectiveness of therapies. We seek to provide an understanding of SDB in NMDs, and in the same light, would like to begin the conversation of thinking about weaning respiratory support when possible.

A breakthrough effect of gene replacement therapy on respiratory outcomes in children with spinal muscular atrophy

“…GRT was administered at a median age of 12 months in SMA-1 patients and at a median age of 22 months in patients with SMA-2. The median follow-up period after receiving GRT for all patients was 23 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) months. All patients were alive at the time of assessment.…”

“…Patients with SMA develop chronic respiratory failure due to progressive muscle weakness 7 . Routine polysomnography is recommended to assess nighttime oxygenation and ventilation and the need for invasive or noninvasive respiratory support 8 .…”

Daytime predictors of nocturnal hypercapnic hypoventilation in children with neuromuscular disorders—The Holy Grail

“…Advances in the description of the natural history of SDB have been made in response to the availability of new treatments for specific NMD. 19 Whilst in DMD the nocturnal features have been associated with the stages of progression of the disease, 7,13 in spinal muscular atrophy the prevalence of SDB has been defined by a relatively small number of studies, and its association with NHH has not been fully clarified. 20,21 In conclusion, the path to the Holy Grail of the perfect predictor to NHH is still quite long.…”

“…Whilst there are common mechanisms contributing to the development of OSA/CSA and NHH, their severity, progression, and associated features may differ. Advances in the description of the natural history of SDB have been made in response to the availability of new treatments for specific NMD 19 …”

Year in review 2021: Neuromuscular diseases

“…The authors proposed that the malnutrition was due to an increased energy expenditure due to chronic respiratory failure and reduced oral intake due to oral muscle weakness and swallowing disorders. This, and other aspects of SBD in neuromuscular disease were reviewed by Gurbani et al 12 In the age of molecular and genetic therapies, the authors highlight the lack of clear metrics to define and evaluate sleep-related respiratory insufficiency in this population. This gap may impede the evaluation of new treatments and their effect on the natural course of the disease.…”