A 77-year-old male was referred to the sleep clinic following a split sleep study at an outside facility showing a mildly increased apnea-hypopnea index of 7.6 events/h but severe arterial oxygen desaturation (low SaO2 60%, 188 minutes with the SaO2 ≤ 88%). The patient reported poor sleep and difficulty breathing when supine for about 6 months. Some mild dyspnea on exertion was noted but the patient was able to play 18 holes of golf using a motorized golf cart.
Several months before the sleep study, the patient was admitted with hypercapnic respiratory failure thought to be due to chronic obstructive pulmonary disease (he had a 40-pack-year history of smoking). An arterial blood gas at discharge with the patient reportedly breathing room air showed a pH of 7.5, PCO2 59.2 mmHg, PO2 73 mmHg, and HCO 45 meq/l.
Physical examination in the clinic showed a body mass index of 27 kg/m2 and awake seated SaO2 of 94% breathing room air. The remainder of the examination was normal except for a crowded oropharynx. An arterial blood gas test after the clinic visit on room air showed a pH of 7.40, PCO2 57 mmHg, PO2 75 mm Hg, and HCO3− 35 meq/l. Chest radiography was normal.
QUESTION: What type of disorder is causing the hypercapnia and severe sleep-related hypoxemia with only a mildly increased apnea-hypopnea index?
ANSWER: Neuromuscular disease with isolated diaphragmatic weakness.
DISCUSSION
Using the arterial blood gas data obtained in the clinic, the alveolar PO2 (PAO2)1,2 = 150 – (57/0.8) = 78.7 mmHg, the computed alveolar–arterial difference (PAO2 – PaO2 = 78.7 – 75 ≈ 4 mmHg) was normal.2 This is incompatible with hypoventilation due to lung disease. The differential diagnosis of such a pattern includes neuromuscular weakness, a chest wall disorder, and abnormal ventilatory control. There was no history of opioid or sedative medication use or reason to suspect a problem with ventilatory control or obesity hypoventilation syndrome (body mass index 27 kg/m2). Spirometry showed a pattern consistent with an extrinsic restrictive defect and respiratory muscle weakness (maximum inspiratory pressure 53 cm H2O). The history of severe orthopnea, yet the ability to ambulate (and play golf), was suggestive of relatively isolated diaphragmatic weakness. A neurology consult was scheduled, and physical examination was near-normal except for mild weakness in the finger extensors and very brisk biceps and patellar reflexes. Electromyography testing revealed findings of neurogenic denervation (fasciculations, polyphasic motor unit potentials with increased amplitude) in multiple muscles in 2 limbs. These findings, together with the presentation and clinical examination, provided evidence of upper and lower motor neuron disease consistent with amyotrophic lateral sclerosis.
Motor neuron disease can rarely present with respiratory failure being the only significant manifestation secondary to diaphragmatic weakness.3–6 Whereas electromyography testing usually finds abnormalities in other muscles, diaphragmatic weakness and the associated symptoms of severe orthopnea are prominent, with relatively preserved strength in the extremities.
In the interval between the initial sleep clinic visit and the completed neurological evaluation, the patient was treated with noninvasive ventilation with volume-assured pressure support and reported the first good night of sleep in the past 5 months.
SLEEP MEDICINE PEARLS
Hypoventilation with preserved oxygenation (normal alveolar–arterial difference) suggests that hypoventilation is not due to lung disease and disorders of the respiratory pump or ventilatory control should be considered. The alveolar–arterial difference increases with age (predicted = 2.5 + 0.21 × age in years).2
Motor neuron disease can present with hypercapnic respiratory failure as the initial manifestation, with severe orthopnea being a clue for the presence of diaphragmatic weakness. The initial neurological examination may be relatively normal.
DISCLOSURE STATEMENT
Both authors participated in the writing and approved the manuscript. Dr. Berry reports being on the Data Safety Monitoring Board for Apnimed and the Scientific Advisory Board for Cerebra Medical. Dr. Wagner reports no conflicts of interest.
Citation: Berry RB, Wagner MH. A golfer with hypoventilation. J Clin Sleep Med. 2024;20(10):1717–1718.
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