Sleep has a physiological influence on respiration, which can have major adverse effects on gas exchange in patients with respiratory insufficiency. These effects relate largely to a reduction in various stimulant inputs to the brainstem respiratory centre. Conditions that may be associated with sleep-related respiratory insufficiency range from pulmonary disorders (such as chronic obstructive pulmonary disease (COPD)), to central respiratory insufficiency (such as central alveolar hypoventilation), neurological and neuromuscular disorders (such as polio and muscular dystrophy), and thoracic cage disorders (such as kyphoscoliosis). All these conditions have in common the finding of hypoxaemia and hypercapnia, which become more pronounced during sleep. The relative hypoventilation, which is common to each condition, is due to varying combinations of an inadequate respiratory drive and an increase in the work of breathing. Management of respiratory insufficiency during sleep should be directed first at optimizing the underlying disorder, then at correcting hypoxaemia with controlled low-flow supplemental oxygen. Pharmacological therapy may be effective in some instances, but the choice of agent varies with the underlying disorder. Assisted ventilation is an important part of the management of advanced cases, and the recent development of intermittent positive pressure ventilation by nasal mask (NIPPV) has been an important advance in this area. Use of NIPPV during the night is associated with beneficial effects during the day, particularly improved awake gas exchange and respiratory muscle strength, in addition to less dyspnoea and improved quality of life. Electrophrenic pacing of the diaphragm is helpful in highly selected cases, particularly patients with central respiratory insufficiency and high quadriplegia, but is frequently complicated by the development of obstructive sleep apnoea.

https://erj.ersjournals.com/content/erj/10/4/920.full.pdf

Impact of sleep in respiratory failure

Motor neurone disease (MND) is a devastating and progressive neurological disorder in which degeneration of motor neurones results in weakness and wasting of the dependent muscles. The prevalence of MND is approximately five per 100 000 and approximately 30% of patients have primary bulbar symptoms.1 Half of the patients die within 36 months of experiencing the first symptom.

Presentation with ventilatory failure is recognised but uncommon,2 occurring in less than 5% of cases3; however, abnormalities of respiratory muscle function are frequently detectable.4 5 As the condition progresses respiratory muscle strength diminishes4 6; indeed, the rate of change in respiratory function is the only measurable parameter which predicts survival.1 When the load placed on the respiratory muscle pump exceeds the capacity of the respiratory muscles, then the patient is at risk of ventilatory failure. Initially abnormalities may be present only in sleep7 or on exercise8 but, frequently, established ventilatory failure ensues. Ventilatory failure is usually manifest by dyspnoea which may be worse on lying flat (if diaphragm weakness is prominent) or sitting upright (if expiratory muscle weakness predominates). More commonly there is generalised weakness and then there are no clear cut postural symptoms. Direct questioning may elicit symptoms suggestive of disordered sleep architecture—for example, daytime somnolence, difficulty concentrating, or “respiratory” nightmares—or carbon dioxide retention—for example, morning headache. Examination may show paradoxical abdominal motion during respiration. This indicates substantial diaphragm weakness9 combined with preservation of enough upper thoracic musculature to generate sufficient negative intrathoracic pressure to cause inward abdominal motion. In more advanced disease paradoxical motion may be difficult to elicit and the patient may simply appear tachypnoeic without useful rib cage movement. In established MND patients may also complain of choking symptoms; most commonly this represents swallowing difficulties. However, if unrelated …

https://thorax.bmj.com/content/thoraxjnl/54/4/367.full.pdf

Ethical and clinical issues in the use of home non-invasive mechanical ventilation for the palliation of breathlessness in motor neurone disease

Patients who are recovering from critical illness may be weak and difficult to wean from ventilatory support as a complication of their underlying disorder, intercurrent events or treatment given during prolonged intensive care. These patients are difficult to assess because of the severity of their weakness and any accompanying encephalopathy. It is essential to undertake a meticulous review, including assessment of any septic, hypoxic or metabolic derangements and a detailed look at the dosage and duration of medication including antibiotics, neuromuscular junction blocking agents and sedation. If a primary underlying neurological cause or an intercurrent event have been excluded, the likeliest cause of weakness is one of the neuromuscular complications of critical care such as: critical care polyneuropathy, an acute axonal neuropathy which develops in patients with preceding sepsis or multi-organ failure; the use of neuromuscular junction blocking agents or steroids; and critical illness myopathy, which is the most common cause of critical care related weakness.

https://pn.bmj.com/content/practneurol/8/5/280.full.pdf

Weakness on the intensive care unit

OBJECTIVE—To characterise the main clinical phenotypes of debrancher deficiency myopathy and to increase awareness for this probably underdiagnosed disorder.
METHODS—The diagnosis of debrancher deficiency was established by laboratory tests, EMG, and muscle and liver biopsy.
RESULTS—Four patients with debrancher deficiency myopathy were identified in the Tyrol, a federal state of Austria with half a million inhabitants. Clinical appearance was highly variable. The following phenotypes were differentiated: (1) adult onset distal myopathy; (2) subacute myopathy of the respiratory muscles; (3) severe generalised myopathy; and (4) minimal variant myopathy. Exercise intolerance was uncommon. The clinical course was complicated by advanced liver dysfunction in two patients and by severe cardiomyopathy in one. All had raised creatine kinase concentrations (263 to 810 U/l), myogenic and neurogenic features on EMG, and markedly decreased debrancher enzyme activities in muscle or liver biopsy specimens. The findings were substantiated by a review of 79 previously published cases with neuromuscular debrancher deficiency.
CONCLUSIONS—This study illustrates the heterogeneity of neuromuscular manifestations in debrancher deficiency. Based on the clinical appearance, age at onset, and course of disease four phenotypes may be defined which differ in prognosis, frequency of complications, and response to therapy.

https://jnnp.bmj.com/content/jnnp/67/3/364.full.pdf

Different clinical aspects of debrancher deficiency myopathy

Spinal muscular atrophy (SMA) is a neurodegenerative disease that has a substantial and multifaceted burden on affected adults. While advances in supportive care and therapies are rapidly reshaping the therapeutic environment, these efforts have largely centered on pediatric populations. Understanding the natural history, care pathways, and patient-reported outcomes associated with SMA in adulthood is critical to advancing health policy, practice and research across the disease spectrum. The aim of this study was to systematically review research investigating the healthcare, well-being and lived experiences of adults with SMA. In accordance with the Preferred Reported Items for Systematic Reviews and Meta-Analysis guidelines, seven electronic databases were systematically searched until January 2020 for studies examining clinical (physical health, natural history, treatment) and patient-reported (symptoms, physical function, mental health, quality of life, lived experiences) outcomes in adults with SMA. Study risk of bias and the level of evidence were assessed using validated tools. Ninety-five articles met eligibility criteria with clinical and methodological diversity observed across studies. A heterogeneous clinical spectrum with variability in natural history was evident in adults, yet slow declines in motor function were reported when observational periods extended beyond 2 years. There remains no high quality evidence of an efficacious drug treatment for adults. Limitations in mobility and daily activities associated with deteriorating physical health were commonly reported, alongside emotional difficulties, fatigue and a perceived lack of societal support, however there was no evidence regarding effective interventions. This systematic review identifies the many uncertainties regarding best clinical practice, treatment response, and long-term outcomes for adults with SMA. This comprehensive identification of the current gaps in knowledge is essential to guide future clinical research, best practice care, and advance health policy with the ultimate aim of reducing the burden associated with adult SMA.

/pdf/health-wellbeing-and-lived-experiences-of-adults-with-sma-a-42ko1mbxci.pdf

Health, wellbeing and lived experiences of adults with SMA: a scoping systematic review

We describe 53 patients who received ventilatory support with a rocking bed. Diagnoses included previous poliomyelitis (30), muscular dystrophy (12), motor neurone disease (4), adult-onset acid maltase deficiency (4) and a miscellaneous group (3). Patients presented with respiratory insufficiency characterized by diaphragm weakness, progressive nocturnal hypoventilation and/or acute or chronic respiratory failure. Domiciliary rocking beds were used by 43 patients for a mean of 16.0 years (range 1 month to 35 years). Most patients were able to breathe adequately by day when sitting or standing, but needed assistance by rocking bed for 6-11 h when lying down for sleep. The rocking bed was well-tolerated, and associated with both symptomatic relief and amelioration of arterial blood gas abnormalities. Seventeen of these 43 patients discontinued its use, either because of discomfort (9) or increasing respiratory insufficiency (8). The rocking bed is a valuable adjunct in the management of the respiratory insufficiency associated with neuromuscular disease.

Use of the rocking bed in the treatment of neurogenic respiratory insufficiency

Summary Twenty-nine patients with a neuronopathic or neuropathic disorder were referred for assessment of respiratory insufficiency between 1978 and 1994. Diagnoses included spinal muscular atrophy (6), chronic idiopathic demyelinating neuropathy (4), Vialetto-van Laere syndrome (3), hereditary motor and sensory neuropathy (3) and a miscellaneous group (5). We also describe seven patients with Guillain-Barre syndrome (GBS) who required longterm ventilatory support for over 6 months to 7 years after the initial illness. Respiratory insufficiency occurred as a consequence of respiratory muscle weakness, impaired bulbar function and restrictive lung defects. In some groups presentation was with progressive nocturnal hypoventilation culminating in acute respiratory failure. Five patients with GBS or chronic idiopathic demyelinating neuropathy were weaned from ventilatory support up to 18 months after the initial illness. The remaining 24 patients required continuous or nocturnal ventilatory support using intermittent positive-pressure ventilation (13), negative pressure ventilation (4), nasal-mask-delivered intermittent positive-pressure ventilation (4), nasal-maskdelivered continuous positive-pressure ventilation

R.M. Chalmers

Papers

Use of the rocking bed in the treatment of neurogenic respiratory insufficiency

Respiratory insufficiency in neuronopathic and neuropathic disorders