Sleep-Disordered Breathing in People with Multiple Sclerosis: Prevalence, Pathophysiological Mechanisms, and Disease Consequences

Abstract

Sleep problems are common in people with multiple sclerosis (MS). Reported prevalence rates of sleep-disordered breathing (SDB) vary between 0 and 87%. Differences in recruitment procedures and study designs likely contribute to the wide variance in reported prevalence rates of SBD in MS. This can make attempts to compare SDB rates in people with MS to the general population challenging. Little is known about the pathophysiological mechanisms that contribute to SDB in people with MS or whether MS contributes to SDB disease progression. However, compared to the general obstructive sleep apnea (OSA) population, there are clear differences in the clinical phenotypes of SDB in the MS population. For instance they are typically not obese and rates of SDB are often comparable or higher to the general population, despite the high female predominance of MS. Thus, the risk factors and pathophysiological causes of SDB in people with MS are likely to be different compared to people with OSA who do not have MS. There may be important bidirectional relationships between SDB and MS. Demyelinating lesions of MS in the brain stem and spinal cord could influence breathing control and upper airway muscle activity to cause SDB. Intermittent hypoxia caused by apneas during the night can increase oxidative stress and may worsen neurodegeneration in people with MS. In addition, inflammation and changes in cytokine levels may play a key role in the relationship between SDB and MS and their shared consequences. Indeed, fatigue, neurocognitive dysfunction, and depression may worsen considerably if both disorders coexist. Recent studies indicate that treatment of SDB in people with MS with conventional first-line therapy, continuous positive airway pressure therapy, can reduce fatigue and cognitive impairment. However, if the causes of SDB differ in people with MS, so too may the optimal therapy. Thus, many questions remain concerning the relationship between these two disorders and the underlying mechanisms and shared consequences. Improved understanding of these factors has the potential to unlock new therapeutic targets.

Sleep Abnormalities in Multiple Sclerosis

“…In addition other articles related to Health and Sleep Physiology were included to support our general arguments. Articles were reviewed by two independent reviewers and a total of 37 articles were selected for inclusion in the present review [4,14,16,17,18,19,22,23,24,25,26,29,31,32,33,34,35,36,37,38,39,41,42,43,49,50,51,53,55,56,61,62,63,64,66,67,70].…”

“…Hypoventilation Syndrome [53]. The seriousness of the disorders is related to the fact that apneas and hypopneas are often associated with cortical arousals disturbing the natural cycle of sleep.…”

“…During the apnea period, diaphragmatic contractions occur until the successful opening of the obstructed airways. In central sleep apnea (CSA), there is an absence of airflow but without any respiratory effort since the problem exists at the respiratory control in the brain [53]. Hypoventilation (Alveolar) syndrome is defined as an elevation in PaCO2 to levels >45 mmHg and associated with hypercapnia and hypoxaemia, which adds to the clinical manifestations and morbidity of the syndrome [54].…”

“…Impact: Sleep-disordered breathing and MS have many overlapping signs and symptoms that are very difficult to separate due to the synergistic nature of them. Sleep-disordered breathing has been documented to affect QoL by causing fatigue and day sleepiness, and to be linked with neurocognitive dysfunction, depression, falls risk and cardiovascular mortality [53].…”

Otolaryngologic Symptoms in Multiple Sclerosis: A Review

“…Simultaneously, intermittent hypoxia could increase oxidative stress and, combined with alterations in hypocapnia sensitivity thresholds, may worsen neurodegeneration in patients with MS, leading to CSA 134,135 . The main cause lies on alterations in the brainstem, which often occur in the late stage of the disease 123 Diagnosis and assessment of SD can be done using polysomnography 137 . Continuous positive airway pressure has been shown to play a significant role in OSA and especially-CSA in MS patients 138 .…”