In amyotrophic lateral sclerosis (ALS), non-invasive ventilation (NIV) is indicated if sleep-disordered breathing (SDB), daytime hypercapnia, or significant diaphragmatic weakness is present. We investigated both short-term and long-term effects of NIV on objective measures of sleep and nocturnal respiration in patients with ALS. Polysomnography (PSG) and transcutaneous capnography were conducted for diagnosis of SDB (T0), for treatment initiation (T1), and follow-up 3, 9, and 15 months later (T2, T3, and T4, respectively). Records from 65 patients were retrospectively analyzed at T0 and T1. At subsequent timepoints, the number of full data sets decreased since follow-up sleep studies frequently included polygraphy rather than PSG (T2, 38 patients, T3, 17 patients, T4, 11 patients). At T0, mean age was 63.2 years, 29 patients were female, and 22 patients had bulbar ALS. Immediate sequelae of NIV initiation included significant increases of slow wave sleep, rapid eye movement sleep, and oxygen saturation. Mean apnea-hypopnea index, respiratory rate, and the maximum transcutaneous carbon dioxide tension were reduced. At T2-T4, normoxia and normocapnia were preserved. Sleep quality measures showed no alteration as diurnal use of NIV gradually increased reflecting disease progression. In contrast to previous reports, improvement of sleep and respiratory outcomes was found in both non-bulbar and bulbar patients. NIV significantly improves objective sleep quality and SDB in the first night of treatment in patients with bulbar and non-bulbar ALS. NIV warrants nocturnal normoventilation without deterioration of sleep quality in the long run with only minor changes to ventilator settings.

In ALS, sleep apnoea is common and often accompanies NH. It is mainly obstructive, and central apnoea appears to be clinically irrelevant. Polygraphy or oxymetry alone are not sufficient to uncover NH. Combination of EMBE and t may increase sensitivity, but transcutaneous capnography is strongly recommended for reliable detection of NH in patients with ALS.

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The significant decline in gonadotropin levels, indicating systemic effects, has to be kept in mind when offering vaginal estriol to breast cancer patients receiving an aromatase inhibitor.

Initiation of NIV using an oronasal interface may be associated with TAO in a subset of patients. Since both EPAP and ∆PAP appear to play a causative role, careful titration of ventilator settings is recommended.

Study Objectives: In neuromuscular disease, non-invasive ventilation (NIV) is indicated if sleep-disordered breathing (SDB) or significant respiratory muscle weakness (RMW) is present. We investigated immediate and long-term effects of NIV on sleep and nocturnal ventilation in patients with late-onset Pompe disease (LOPD). Methods: Polysomnography and transcutaneous capnometry were performed in 22 adult patients. If indicated, NIV was initiated the subsequent night and follow-up sleep studies were scheduled. Sleep quality and health-related quality of life (HRQoL) were self-assessed using standard questionnaires. Results: Fourteen patients received enzyme replacement therapy (ERT), five patients were treatment-naïve, and three individuals had previously stopped ERT. Fifteen patients reported symptoms of SDB, all showing abnormal sleep studies. Two patients had obstructive sleep apnea (OSA), three patients showed both OSA and nocturnal hypercapnia, four individuals had nocturnal hypercapnia, and two patients had both OSA and daytime hypercapnia. Four patients showed normal apnea-hypopnea index and CO 2 measures but nocturnal tachypnea, orthopnea, and significant RMW were present. Supine forced vital capacity (FVC) and positional drop of FVC were independent predictors of SDB. In patients with SDB, HRQoL was significantly reduced. NIV was initiated in 15 individuals and led to significant improvement of ventilation and oxygenation in the first night of treatment. Follow-up sleep studies revealed stable normoxia and normocapnia without deterioration of sleep outcomes for up to 40 months. Conclusions: In LOPD, SDB is common and comprises both hypoventilation and OSA. NIV significantly improves respiration already in the first night of treatment. NIV warrants nocturnal long-term normoventilation without deterioration of sleep quality. Keywords: noninvasive ventilation, polysomnography, Pompe disease, respiratory muscle weakness, sleep-disordered breathing Citation: Boentert M, Dräger B, Glatz C, Young P. Sleep-disordered breathing and effects of noninvasive ventilation in patients with late-onset Pompe disease. J Clin Sleep Med 2016;12(12):1623-1632. I NTRO DUCTI O NPompe disease is an autosomal recessive lysosomal storage disorder caused by deficiency of the α-1,4-glucosidase (GAA) enzyme. Glycogen accumulation results in lysosomal dysfunction, autophagy, and progressive tissue damage.1 Early infantile-onset Pompe disease is characterized by quadriplegia and fatal hypertrophic cardiomyopathy if enzyme replacement therapy (ERT) is not available. The term late-onset Pompe disease (LOPD) comprises subtypes with late-infantile, childhood, juvenile, or adult disease manifestation. LOPD lacks major cardiac involvement and is characterized by progressive myopathy of the limb-girdle muscles, the trunk muscles, and the diaphragm.2 Respiratory muscle weakness manifests as nocturnal hypoventilation first, eventually leading to sleep disruption, morning headache, fatigue, and excessive daytime sleepiness.3 In addition, patients...

Objective In amyotrophic lateral sclerosis (ALS), respiratory muscle involvement and sleep-disordered breathing relate to worse prognosis. The present study investigated whether respiratory outcomes on first-ever sleep studies predict survival in patients with ALS, specifically taking into account subsequent initiation of non-invasive ventilation (NIV). Methods From patients with ALS, baseline sleep study records, transcutaneous capnometry, early morning blood gas analysis, survival data and clinical disease characteristics were retrospectively analyzed. Patients were stratified according to whether enduring NIV was consecutively established (“NIV(+)”) or not (“NIV(–)”). Results Among the study cohort (n = 158, 72 female, 51 with bulbar onset ALS, 105 deceased) sleep-disordered breathing was present at baseline evaluation in 97 patients. Early morning base excess (EMBE) > 2 mmol/l predicted nocturnal hypercapnia. Ninety-five patients were NIV(+) and 63 were NIV(–). Survival from baseline sleep studies was significantly reduced in NIV(–) but not in NIV(+) patients with nocturnal CO2 tension ≥ 50 mmHg, apnea hypopnea index ≥ 5/h, and EMBE > 2 mmol/l. Hazard ratio for EMBE > 2 mmol/l was increased in NIV(–) patients only, and EMBE independently predicted survival in both NIV(–) and NIV(+) patients. Furthermore, EMBE on baseline sleep studies was the only predictor for survival from symptom onset, and hazard ratio for shorter survival was markedly higher in the NIV(–) than the NIV(+) group (2.85, p = 0.005, vs. 1.71, p = 0.042). Interpretation: In patients with ALS, EMBE > 2 mmol/l predicts nocturnal hypercapnia and shorter survival. Negative effects of sleep-disordered breathing on survival are statistically abolished by sustained NIV.

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