0995 Sleep-related Hypoventilation in a 62-Year-Old Female with a Rare Genetic Neuromuscular Disorder

Abstract

Abstract Introduction Central Core Myopathy (CCM) is a rare genetic neuromuscular disorder involving a mutation in the ‘Ryanodine Receptor’ (RyR1) gene, also known as the gatekeeper of calcium within the muscle cells. CCM typically manifests as slowly progressive proximal muscle weakness Currently, there is limited data regarding the management of nocturnal hypoventilation in adults with neuromuscular disorders. Report of case(s) We present a 62-year-old woman with CCM, as identified via RyR1 mutation (c14818G>A) on genetic testing, as well as muscle biopsy. This genotype is associated with < 10% respiratory muscle involvement. She presented to the sleep clinic with complaints of morning headaches, non-restorative sleep, and daytime sleepiness. Her polysomnogram (PSG) showed an overall Apnea-Hypopnea-Index in the normal range. However, there was a progressive increase in transcutaneous carbon dioxide levels (PtcCO2), reaching a peak of 53 mmHg during rapid eye movement (REM) sleep from 38 mmHg during wakefulness, consistent with sleep-related neuromuscular hypoventilation. On further evaluation, this patient had no evidence of neuromuscular restrictive lung physiology or overt diaphragmatic dysfunction, as suggested by < 20% variation in the supine forced vital capacity. Moreover, her negative inspiratory force (NIF) value was not less than negative 40. However, in the setting of her sleep-related symptoms and evidence of nocturnal hypoventilation, our team decided to trial non-invasive positive pressure ventilation (NIPPV). Since we had concerns about respiratory alkalosis in NREM sleep in the setting of normal body mass index, normal pulmonary function tests, and hypoventilation limited to REM sleep, the patient was sent for in-lab titration of pressures with measurement of PtcCO2 to appropriately recommend NIPPV settings. The study demonstrated bi-level positive airway pressure settings of IPAP 7 cmH20, EPAP 5 cmH20, and a backup rate of 12/min resulting in sustained eucarbia and steady PtcCO2 levels during both REM and NREM sleep. Conclusion This case highlights the importance of evaluation for nocturnal hypoventilation in symptomatic patients with rare neuromuscular disorders and the potential for symptomatic improvement with treatment with NIPPV. Moreover, the case demonstrates the importance of in-lab titration of pressure settings for NIPPV when hypoventilation is limited to REM sleep, due to concern for iatrogenic hyperventilation and respiratory alkalosis. Support (if any)