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Impaired pharyngeal reflex responses to negative pressure: A novel cause of sleep apnea in multiple sclerosis.

Obstructive sleep apnea (OSA) is common in people with multiple sclerosis (MS). However, people with MS often do not have 'typical' anatomical risk factors (i.e. non-obese and female predominance). Accordingly, non-anatomical factors such as impaired upper airway muscle function may be particularly important for OSA pathogenesis in MS. Therefore, this study aimed to investigate genioglossus (largest upper-airway dilator muscle) reflex responses to brief pulses of upper airway negative pressure in people with OSA and MS. 11 people with MS and OSA and 10 OSA controls without MS matched for age, sex and OSA severity were fitted with a nasal mask, pneumotachograph, choanal and epiglottic pressure sensors and intramuscular electrodes into genioglossus. Approximately 60 brief (250ms) negative pressure pulses (~-12cmH2O mask pressure) were delivered every 2-6 breaths at random during quiet nasal breathing during wakefulness to determine genioglossus EMG reflex responses (timing, amplitude and morphology). Where available, recent clinical MRI brain scans were evaluated for the number, size and location of brainstem lesions in the MS group. When present, genioglossus reflex excitation responses were similar between MS participants and controls (e.g. peak excitation amplitude 229±85 vs. 282±98 % baseline, p=0.17). However, ~30% of people with MS had either an abnormal (predominantly inhibition) or no protective excitation reflex. Participants with MS without a reflex had multiple brainstem lesions including in the hypoglossal motor nucleus which may impair sensory processing and/or efferent output. Impaired pharyngeal reflex function may be an important contributor to OSA pathogenesis for a proportion of people with MS.