Effects of Sleep-Related Disorders on the Prognosis of Amyotrophic Lateral Sclerosis

Abstract

Background/Objective: In this study, we demonstrated the effects of obstructive sleep apnea syndrome (OSAS) on the prognosis of amyotrophic lateral sclerosis (ALS). However, the effects of sleep-related disorders other than breathing problems are still waiting to be delineated. Methods: In this longitudinal retrospective and prospective study, we investigated 73 patients with ALS compared to 20 healthy subjects, to determine sleep-related disorders and their impact on disease prognosis. Results: In patients with ALS, the mean respiratory disturbance index (RDI) was 28.0/h, which was significantly higher than that in the controls (p < 0.001). OSAS was present in 67% of the patients, sleep-related hypoxemia was observed in 13.7% of the patients, and 5.4% had central sleep apnea syndrome. In patients with bulbaronset disease, higher RDI was almost significantly associated with lower survival (p = 0.056). The mean index of periodic leg movements in sleep was significantly higher in patients with ALS (34.0 ± 19.9/h) than that in the controls (12.5 ± 15.5/h; p < 0.001). Periodic leg movements disorder (PLMD) was diagnosed in 23 patients with ALS (31.5%); fragmentary myoclonus was present in 13.7% of patients, and REM-sleep behavior disorder was diagnosed in 4 patients (5.4%). The presence of PLMD in addition to OSAS was significantly associated with worse prognosis and poorer survival (p = 0.040). Conclusions: These findings emphasize that sleeprelated disorders other than OSAS deserve attention in ALS. ALS is a catastrophic and frustrating disease for both patients and physicians; thus, the diagnosis and treatment of comorbid sleep disorders could improve the survival of patients with ALS.

Sleep Disorders in Patients with Neurologic Disease

“…All people with neuromuscular disorders at risk for ventilatory insufficiency should undergo pulmonary function testing; red flags for impending impaired breathing include a forced expiratory volume in 1 second less than or equal to 40% predicted, forced vital capacity less than 1.5 liters, a greater than 25% reduction in seated-to-supine vital capacity, and a significant reduction from baseline in maximal inspiratory pressure, maximal expiratory pressure, or sniff nasal pressure, with reference ranges dependent on sex, body mass index, and age 67 . In-laboratory overnight polysomnography with noninvasive carbon dioxide monitoring (eg, transcutaneous carbon dioxide monitors) is considered the gold standard diagnostic test to confirm sleep-related hypoventilation in people with neuromuscular and chest wall disorders; alternatively, treatment may be initiated empirically with settings adjusted based on response and arterial blood gas measurements.…”

REM Sleep Behavior Disorder and Other REM Parasomnias

“…29 Other neurologic diseases that are uncommon causes of RBD include multiple sclerosis, stroke, tumors, Wilson disease, Huntington disease, autoimmune disorders such as anti-IgLON5, contactin-associated protein-like 2, and leucine-rich glioma-inactivated 1 antibody diseases, and amyotrophic lateral sclerosis. 32,33 Posttraumatic stress disorder (PTSD) is also linked to RBD. RBD occurs in 15% of veterans with PTSD, 34 and RWA is more prominent in people who have PTSD with RBD compared with those who have PTSD without RBD but is less prominent than in isolated RBD.…”

“…Other neurologic diseases that are uncommon causes of RBD include multiple sclerosis, stroke, tumors, Wilson disease, Huntington disease, autoimmune disorders such as anti-IgLON5, contactin-associated protein-like 2, and leucine-rich glioma-inactivated 1 antibody diseases, and amyotrophic lateral sclerosis 32,33 . Posttraumatic stress disorder (PTSD) is also linked to RBD.…”

Sleep and Sleep Disruption in Amyotrophic Lateral Sclerosis

“…Own unpublished data suggest that the PLM index is increased in a large subset of patients but does not translate into associated arousals from sleep [51•]. A recent study postulated PLM disorder to be present in almost one-third of ALS patients but ICSD-3 diagnostic criteria were possibly not fully met, and association with sleep arousals was not reported [52]. Pathophysiologically, it may be hypothesized that in ALS, PLM reflect spinal cord disinhibition due to degeneration of descending central pathways [53].…”