Factors Associated With Poor Sleep Quality
Sleep quality was not associated with age, sex, duration of ALS symptoms, type of ALS at disease onset, daytime sleepiness (ESS), body mass index, ALSFRS, ALSFRS bulbar subscore, FVC, or MIP. There was no difference in PSQI based on the ALSFRS at different severity cutoffs. Sleep quality was correlated with symptoms of depression. There was a positive correlation between the PSQI and BDI II scores, r = 0.344 (P = 0.024) (Fig. 1). The mean BDI II score was 11.3 ± 6.7, with 10 (23%) patients having mild symptoms and 5 (12%) patients having moderate symptoms of depression. The mean BDI II score was 13.7 ± 6.5 in poor sleepers versus 7.8 ± 5.3 in good sleepers (P = 0.004). Although sleep quality was not associated with functional status as assessed by the ALSFRS score, the patient's ability to turn in bed and adjust bed clothes was associated with poor sleep quality, r = −0.335 (P = 0.033). Ten (23%) patients were unable to or experienced great difficulty performing this task. These patients had a mean PSQI of 9.7 ± 4.9 compared with patients who performed the task normally or slowly and clumsily but without help (score 3–4) who had a mean PSQI score 6.6 ± 3.5 (P = 0.035).
Patients tended to under-recognize their poor sleep quality. Despite the high global PSQI scores, when asked to rate their sleep quality overall, 37 (86%) patients reported their overall sleep quality as very good or fairly good.
Excessive Daytime Sleepiness
Despite a high prevalence of poor sleep quality, few patients noted excessive daytime sleepiness on the ESS. Six (14%) patients and 2 (5%) controls had ESS >9 (P = 0.265). Mean ESS in the patients with ALS was 6.6 ± 3.0, which was higher compared with a mean ESS of 5.0 ± 3.1 in controls (P = 0.020). Daytime sleepiness was not associated with sleep quality but was associated with respiratory muscle weakness, with a negative correlation between the ESS and the FVC, r = −0.371 (P = 0.016), and between the ESS and the MIP, r = −0.341 (P = 0.031) (Fig. 2). Among patients with FVC <70% predicted, the mean ESS was 7.7 ± 2.9, which was higher compared to patients with FVC ≥70% predicted, 5.4 ± 2.7 (P = 0.012).
In our study, we demonstrated poorer sleep quality in patients with ALS at the time of diagnosis compared with controls. In patients with ALS, poor sleep quality was associated with symptoms of depression and limited mobility in bed. Although few patients reported excessive daytime sleepiness, this was associated with respiratory muscle weakness.
Several studies have showed that poor sleep quality is frequent in patients with ALS. In a group of 20 patients with ALS starting NIV, average PSQI was 8, similar to our study.6 Lo Coco et al performed a detailed sleep evaluation in 100 patients with ALS and reported a mean PSQI score of 6.8 ± 4.0, with 59% of patients classified as poor sleepers,9 and poor sleep quality was associated with ALSFRS-R, ESS, and BDI scores. In contrast to our study, these investigators examined patients who had longer disease duration and greater impaired motor function, including patients using NIV and enteral nutrition. The similar poor sleep quality results in both studies and the shorter ALS disease duration (14.9 ± 7.1 months) in our study suggest that self-reported poor sleep quality may be an early symptom in patients with ALS.
Mild to moderate depressive symptoms were reported by one-third of our patients and was the major factor associated with poor sleep quality. Kurt et al21 describe a wide range of reported prevalence of depression in patients with ALS, and a rate of 9–11% with the use of structured interviews. Sleep disturbances such as insomnia or hypersomnia are well-known symptoms of depression, and patients with depression have poorer sleep quality than controls.17 Conversely, increased sleep disturbance such as insomnia or hypersomnia may precede the onset of depression;22 thus, the relationship between mood and sleep is complex and often bidirectional. It is unclear whether depression is the cause of poor sleep quality in patients with ALS.
Most of our patients did not have sleep onset insomnia or abnormal sleep duration. The primary sleep disturbances were impaired sleep maintenance and postural discomfort, which have been previously noted in patients with ALS. Studies have demonstrated that patients with ALS wake multiple times a week, in the middle of the night or morning, and/or have difficulty turning in bed or adjusting bed clothes.9
Of note, daytime sleepiness was not a prominent feature of the disturbed sleep pattern in most patients. When this symptom was present, it was associated with respiratory muscle weakness and was not associated with self-reported sleep quality. In patients with chronic obstructive pulmonary disease, a high frequency of self-reported poor sleep quality was also not associated with excessive daytime sleepiness.23 Similarly, other patients with ALS have been noted to have poor sleep quality without excessive daytime sleepiness.6 Thus, excessive daytime sleepiness is not always a sensitive marker of poor sleep quality.
In the patients with ALS, there was mild to moderate respiratory muscle weakness as estimated by FVC and MIP that correlated with daytime sleepiness. Bulbar dysfunction in patients with ALS can cause upper airway narrowing or closure secondary to weakness of the abductor muscles and add an additional load to the respiratory system. This in turn could result in nocturnal hypoventilation leading to nocturnal arousals/awakenings, sleep fragmentation, and sleep maintenance insomnia. Sleep fragmentation may be responsible for excessive daytime sleepiness. Our findings are similar to those in previous studies that showed a correlation between the ESS score and respiratory muscle strength in patients with ALS.5,24
In our study, patients with ALS tended to underestimate their poor sleep quality. Most patients rated their overall sleep quality as good despite high PSQI scores consistent with poor sleep quality. The cause for this discordant finding is not well understood. One possibility is that patients might be overwhelmed by the prominent loss of motor function and physical disability and might neglect their nocturnal symptoms. Another possibility is that patients with ALS maintain quality of life even with disease progression by adapting their expectations of daily life, and this could extend to sleep time.25 Without a structured sleep assessment, the significant sleep disturbances that are present in these patients may be under recognized.
Our single-center study has several limitations. We examined patients recently diagnosed with ALS, which is not synonymous with symptom onset. Patients with ALS are evaluated in a multidisciplinary ALS clinic after varying disease duration and having disparate symptoms. The delay from the time of symptom onset until diagnosis remains unacceptably long.26 However, evaluating sleep at diagnosis is currently the best available surrogate for understanding sleep disorders early in the course of ALS. Sleep quality and excessive daytime sleepiness measures were based on data from questionnaires and were the only measures compared between patients with ALS and controls. Objective studies of sleep and nocturnal respiration such as polysomnography were not performed at the time of disease diagnosis. Because of the cross-sectional nature of the study, our findings are limited to only one time point. It is possible that sleep quality fluctuates during the course of the disease due to adaptations to motor impairment by the patients, implementation of pharmacological and nonpharmacological interventions, disease progression,27 initiation of NIV therapy,6 and variability of symptoms from month to month such as depression.28 Although we focused on patients with newly diagnosed ALS, it is not uncommon for patients to have varying disease duration and symptomology before their diagnosis.1 To account for some of this variability in our study, we examined relationship between sleep quality and symptom duration and did not find an association. There is also the possibility that some of the sleep symptoms preceded the onset and/or diagnosis of ALS and are unrelated to the disease.
Our findings lead us to believe that poor sleep quality in patients with ALS at the time of diagnosis is likely multifactorial. It is possible that those patients who have impaired respiratory function also have nocturnal hypoventilation and present with more daytime sleepiness. Other contributing factors may include nocturnal postural discomfort, limited mobility, depressive symptoms, or sometimes a combination of several factors. It is important to determine the underlying causes of poor sleep quality in patients with ALS to tailor-specific interventions to each patient.
This study emphasizes the importance of assessing sleep quality and disturbances in patients with ALS. ALS practice parameters recognize insomnia as common in ALS, but no specific recommendations are made for its treatment because of a lack of evidence. However, recently interventions such as NIV therapy have been shown to improve sleep quality6 providing one therapeutic option to improve sleep in at least some patients with ALS and an additional potential indication for the use of NIV. Because there is no effective cure for ALS, the goal is to palliate symptoms.1 Hence, attention to sleep quality should be part of this comprehensive symptom-based care.
In conclusion, patients with newly diagnosed ALS have a high frequency of self-reported poor sleep quality that was associated with symptoms of depression and difficulty turning in bed. Despite significant sleep disturbances, few patients reported excessive daytime sleepiness, which was associated with respiratory muscle weakness. Given the high prevalence of poor sleep in these patients, longitudinal studies to examine the evolution of sleep quality and the effectiveness of individualized interventions are needed in patients with ALS.
The authors thank the ALS Association and the DC/MD/VA Chapter for the continued support of the University of Maryland ALS Center of Excellence and our patients.
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Keywords:Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved
amyotrophic lateral sclerosis; sleep quality; depression; limited mobility