Sleep-disordered breathing in neuromuscular disease

Cardiac abnormalities

Lastly, it should be noted that diseases such as the muscular dystrophies, myotonic dystrophy, mitochondriopathies, and nemaline myopathy can be associated with a cardiomyopathy ,which can lead to central sleep apnea in the form of Cheyne-Stokes breathing.

Sleep-disordered breathing in specific NMDs

In amyotrophic lateral sclerosis (ALS), up to 75% of patients may have SDB, the majority of which is central sleep apnea (CSA) and hypoventilation although they still have a higher prevalence of obstructive sleep apnea (OSA) than the general population. Whether the diaphragm or the pharyngeal muscles are predominantly affected may have something to do with the type of apnea a patient experiences; however, studies have shown that even in bulbar ALS, CSA is most common. It should be noted, that this is not Cheyne-Stokes CSA, but rather lack of chest wall and abdominal movement due to weakness. (David WS, et al. J Neurol Sci. 1997;152[suppl 1]:S29-35).

In myasthenia gravis (MG), about 40% to 60% of patients have SDB, and about 30% develop overt respiratory weakness, generally late in the course of their disease. Many of these patients report excessive daytime sleepiness, often attributed to myasthenic fatigue requiring treatment with corticosteroids. It is important to evaluate for sleep apnea, given that if diagnosed and treated, their generalized fatigue may improve and the need for steroids may be reduced or eliminated altogether. It is also important to note that the respiratory and sleep issues MG patients face may not correlate with the severity of their overall disease, such that patients well-controlled on medications from a generalized weakness standpoint may still require home noninvasive ventilation (NIV) for chronic respiratory failure due to weakness of the respiratory system muscles.

Duchenne muscular dystrophy (DMD), an X-linked disease associated with dysfunction of dystrophin synthesis, is often diagnosed in early childhood and gradually progresses over years. Their initial sleep and respiratory symptoms can be subtle and may start with increased nighttime awakenings and daytime somnolence. Generally, these patients will develop OSA in the first decade of life and progress to hypoventilation in their second decade and beyond. These patients are especially important to recognize, as studies have shown appropriate NIV therapy may significantly prolong their life (Finder JD, et al; American Thoracic Society. Am J Respir Crit Care Med. 2004(Aug 15);170[4]:456-465).

In addition to the well-known motor neuron and neuromuscular diseases mentioned above, neuropathic diseases can lead to sleep disturbances, as well. In Charcot-Marie-Tooth (CMT), pharyngeal and laryngeal neuropathy, as well as hypoglossal nerve dysfunction, lead to OSA. Similar to ALS and MG, there is a significant amount of CSA and hypoventilation, likely related to phrenic neuropathy. In contrast to MG, in CMT, the severity of neuropathic disease does correlate to the severity of sleep apnea.

Testing

Testing can range from overnight oximetry to polysomnogram (PSG) with CO₂ monitoring. Generally, all patients with a rapidly progressive neuromuscular disease should get pulmonary function testing (PFT) (upright and supine) to evaluate forced vital capacity (FVC) every 3 to 6 months to monitor for respiratory failure. Laboratory studies that can be helpful in assessing for SDB are the PaCO₂ (> 45 mm Hg) measured on an arterial blood gas and serum bicarbonate levels (>27 mmol/L or a base excess >4 mmol/L). Patients can qualify for NIV with an overnight SaO₂ less than or equal to 88% for greater than or equal to 5 minutes in a 2-hour recording period, PaCO₂ greater than or equal to 45 mm Hg, forced vital capacity (FVC) < 50% of predicted, or maximal inspiratory pressure (MIP) <60 cm H₂O. For ALS specifically, sniff nasal pressure < 40 cm H₂O and orthopnea are additional criteria that can be used. It is worth noting that a PSG is not required for NIV qualification in neuromuscular respiratory insufficiency. However, PSG is beneficial in patients with preserved PFTs but suspected of having early nocturnal respiratory impairment.