Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the relentless loss of both central and peripheral motor neurons. This degeneration inevitably leads to generalized muscle weakness, resulting in premature death.

Sleep disturbances are highly prevalent in ALS patients, exerting a profound impact on both patients and their caregivers. These disturbances stem from a range of physical symptoms, including muscle cramps, pain, reduced mobility, spasticity, mucus retention, and restless legs syndrome. Additionally, a notable proportion of ALS patients grapple with depression and anxiety, which significantly contribute to insomnia. A smaller subgroup of ALS patients experiences rapid eye movement (REM) sleep Behavioral disorder, reflective of the neurodegeneration of central nervous system pathways implicated in REM sleep regulation. While numerous studies have explored sleep patterns and clinical factors linked to sleep disruption in ALS, precise prevalence figures remain elusive.

With regard to overall prognosis, the presence of sleep-disordered breathing (SDB) and nocturnal hypoventilation (NH) emerges as a matter of paramount concern. This is chiefly because NH precedes the onset of respiratory failure. Obstructive sleep apnea (OSA) is a prevalent condition in ALS patients, resulting from upper airway hypotonia and muscle weakness, which can lead to a significant reduction in airway lumen. It is also essential to underscore the profound secondary cardiopulmonary consequences of chronic nocturnal hypoxemia, including pulmonary hypertension, right heart failure, arrhythmia, an elevated risk of stroke, myocardial infarction, and other associated complications.

Given the absence of curative treatments for ALS, it is imperative to investigate sleep-related complaints rigorously to uncover any treatable etiologies and enhance or stabilize patients' quality of life as much as possible. This underscores the critical importance of early diagnosis and intervention for sleep-disordered breathing in ALS, particularly given the dramatic reduction in lifespan associated with this disease. Moreover, recognizing respiratory sleep disorders can serve as an indication for the initiation of Non-Invasive Ventilation (NIV) in the early stages of ALS. NIV is a well-established intervention known to alleviate symptoms of sleep disturbance, enhance overall quality of life, and improve cognitive function. It is primarily indicated in cases of sleep-disordered breathing and inspiratory muscle dysfunction. Notably, it has been demonstrated that the survival time of patients receiving home ventilatory support depends on the attainment of normocapnia, normoxia, and the elimination of apneic and hypopneic events during sleep.

Study Design and Data Collection

We conducted a retrospective study to investigate respiratory sleep disturbances in ALS patients. Our cohort consisted of ALS patients who attended Pulmonology consultations over a 23-month period, and we selected those with valid sleep studies. The study aimed to distinguish ALS patients with sleep apnea (SA) from those without SA. Data were extracted from medical records, including patient demographics, clinical history, and intervention.

Statistical Analysis

Descriptive statistics were utilized to summarize patient characteristics and respiratory-sleep disturbances, primarily focusing on SA. Categorical variables are presented as frequencies and percentages, while continuous variables are expressed as means with standard deviations.

Patient Characteristics

In our study, we identified 46 ALS patients, of which 32 had valid samples. The majority of these patients presented with respiratory/sleep-related symptoms at their initial consultation (75%). Seventy-five percent of the patients were diagnosed with sleep apnea, primarily obstructive sleep apnea.

SA-ALS phenotype

Differentiating between SA-ALS and Non-SA-ALS patients, we observed notable differences that are listed in the next table.

Table 1: Differentiating between SA-ALS and Non-SA-ALS patients.

^*1 Patient initiated because of FVC<70% and 1 patient because of acute respiratory failure.

Notably, 23% of patients exhibited mild sleep apnea, 21% presented with moderate sleep apnea, and 21% had severe sleep apnea. Furthermore, the mean body mass index (BMI) varied in correlation with the severity of sleep apnea within this patient group. Among patients with mild sleep apnea, the mean BMI was 23 Kg/m². For those with moderate sleep apnea, the mean BMI increased to 30 Kg/m², and the group with severe sleep apnea displayed an even higher mean BMI of 37 Kg/m².

Additionally, the mean duration of time with peripheral oxygen saturation under 90% (T90) also exhibited significant differences when categorized by the severity of IAH. For patients with mild sleep apnea, the T90 was 15%, indicating a relatively lower degree of nocturnal oxygen desaturation. In contrast, the group with moderate sleep apnea had a T90 of 31%, signifying more extended periods of oxygen saturation below the 90% threshold. Lastly, the severe sleep apnea group displayed a substantially higher T90 of 70%, indicative of more severe nocturnal oxygen desaturation.

These findings highlight the heterogeneity within the SA-ALS phenotype, revealing variations in BMI and T90 based on the severity of sleep apnea. This characterization underscores the complex interplay of factors within this patient subgroup.

NIV

NIV was initiated in 22 patients (69%), with the majority belonging to the SA-ALS group (n=20). In two cases, NIV was introduced for reasons other than SA - one initiated because of FVC<70% in respiratory functional study and other during an episode of acute respiratory failure.

Mortality

During the follow-up period, 17 patients (36%) passed away. A higher prevalence of mortality was observed among male patients, accounting for 82% of the deceased cases.

Our study underscores the common occurrence of respiratory and sleep-related symptoms in ALS patients at the time of their initial evaluation. Furthermore, the presence of SA, particularly OSA, significantly impacts their lives, sleep quality, and overall quality of life.

Our study adds to the limited existing data on respiratory-sleep disturbances in ALS. We identified distinct characteristics in the SA-ALS phenotype based on BMI, presence of symptoms, T90 values, and NIV use. This preliminary study emphasizes the need for further investigations to gain deeper insights into the presence and impact of respiratory-sleep disturbances in the complex and progressive disease that is ALS.

We wish to acknowledge the ALS patients and their families for their cooperation and the healthcare professionals at our clinic for their dedicated support throughout this study.

Funding Information

This study was conducted without external funding.

1. Quaranta VN, Carratu P, Damiani MF, Dragonieri S, Capozzolo A, Cassano A, et al. The Prognostic Role of Obstructive Sleep Apnea at the Onset of Amyotrophic Lateral Sclerosis. Neurodegenerative Diseades. 2017; 17: 14-21.
2. Boentert M. Sleep disturbances in patients with amyotrophic lateral sclerosis: current perspectives, Nature and Science Sleep. 2019; 11: 97-111.