Upper Airway Nerve Lesions in Obstructive Sleep Apnea

Eva Svanborg, Ph.D.

Department of Neuroscience and Locomotion/Division Clinical Neurophysiology, Faculty of Health Sciences, University of Linköping, Linköping, Sweden

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The histories of many patients with obstructive sleep apnea syndrome (OSAS) reveal a gradual onset starting with habitual snoring, often rather early in life. OSAS is also an unusual diagnosis before middle age. The progressive nature of the disease has been confirmed in some studies of untreated mild- moderate cases (1, 2). The etiology of OSAS is only partly known. The most obvious pathogenic factor is a narrow upper airway due to enlarged tonsillar tissue, skeletal anomalies, or fat deposits. Weight increase often provokes impairment of obstructive respiration but does not always explain progression. Marked worsening of obstructive breathing has been found in some patients experiencing weight reduction (1), and in another study (2), there was no association between changes in weight and apnea index. After adolescence, the tonsils gradually become smaller, and the facial skeleton is usually not altered in adulthood. Another factor that changes over time must be responsible for disease progression.

Longstanding employment requiring the use of vibrating tools can cause local nerve lesions in the hands (3). Snoring vibrations every night could cause neuronal lesions in the upper airway, which, in turn, cause gradual collapse due to muscular weakness and/or impaired reflex mechanisms. An injury of this cause should involve both motor and sensory fibers, and there is indeed today evidence that both these types of lesions exist in patients with OSAS.

The patency of the upper airway during inspiration is maintained by the dilating muscles. These are activated by a reflex mechanism as a reaction to the negative intrapharyngeal pressure, probably mediated by intra- or submucosal mechanosensory receptorsa hypothesis supported by the fact that topical anesthesia of the upper airway induces apneas in snorers and normal subjects (4). To investigate sensory nervous function, Larsson and coworkers (5) tested temperature thresholds of the tonsillar pillars of nonsnoring control subjects and patients with OSAS. Significant differences were found; some patients with OSAS were completely unable to differentiate between heat and cold. At the tip of the tongue, no differences were found, indicating a very local sensory dysfunction. Friberg and colleagues (6) tested vascular reactivity in the soft palatal mucosa, using electrical stimulation. The normal response is vasodilatation. This reaction was exaggerated in habitual snorers compared with normal control subjects, whereas patients with OSAS exhibited a marked reduction in reactivity. The latter finding could be explained by almost complete loss of afferent C fibers. The exaggerated reaction of snorers could be the result of minor lesions with consequent reinnervation, because increased sensitivity to mechanical stimuli may then ensue. Moreover, an increased density of sensory nerve terminals with abnormal localization and appearance was found in the soft palatal mucosa of nine of 10 patients with OSAS and in four of 11 snorers, and was not present in nonsnoring control subjects (7). The pharyngeal swallowing function is also dependent on adequate sensitivity, and dysfunction has been demonstrated in both patients with OSAS and snorers without subjective dysphagia; remission occurs after uvulopalatopharyngoplasty (8).

In this issue of the Journal (pp. 250-255), Kimoff and coworkers (9) have further substantiated sensory dysfunction, studying two-point discrimination and vibratory sensation in the upper airway, in patients with OSAS and nonapneic snorers compared with nonsnoring control subjects. There was no significant difference between snorers and patients with OSAS. When 16 patients with OSAS were retested after continuous positive airway pressure (CPAP) treatment, vibration thresholds had significantly improved. This, to my knowledge, is the first evidence that CPAP treatment may to some extent act curatively, and not just relieve symptoms. However, recovery of sensory function was not complete, because two-point discrimination did not change despite treatment. This is consistent with the fact that relapse of OSA usually takes place when CPAP treatment is interrupted.

Vibration thresholds reflect the functional integrity of the largest afferent sensory fibers, and vibrametry is usually employed to diagnose polyneuropathy. Circumscribed cutaneous neuronal lesions are usually not tested because of the risk of stimulus propagation to adjacent, normally innervated tissue. It is therefore interesting that a localized lesion could be verified by this technique in the present study.

The sensory dysfunction in the previously mentioned studies could, at least partly, have been caused by mucosal edema, which is common in the oropharynx of snorers. There is, however, also evidence of motor neuron lesions, which could not result from this cause. Such lesions could be responsible for a partial paresis of the dilating muscles. In an electron microscopic study, Woodson and coworkers (10) found degenerative changes in neurons from the soft palate and uvula of patients with OSAS. Friberg and colleagues (11) compared biopsies of musculus palatopharyngeus from nonsnoring controls, habitual snorers, and patients with OSAS. The degree of muscle pathology increased in parallel with the proportion of obstructive breathing during sleep. All the patients with OSAS exhibited histological abnormalities, including signs specific for motorneuron lesions.

It might seem contradictory that augmented activity of the genioglossus muscle has been recorded in awake patients with OSAS. However, this activity is markedly diminished during sleep, the difference being greater than in normal subjects. The increased muscle activity has been interpreted as a compensation for a narrow pharyngeal airway, lost during sleep secondary to the physiological muscle hypotonia in that state (12). Augmented genioglossus activity could, however, be a compensatory mechanism, not only for anatomical factors but also for partial paresis of other dilating or stabilizing muscles, which are more exposed to snoring vibrations than is the tongue muscle.

These studies support the hypothesis that upper airway afferent and efferent nerve lesions are present in some patients with snoring, and in most patients with OSAS. There is currently no clear-cut proof that these lesions increase in parallel with the clinical progression from habitual snoring to OSAS, although this may depend on the small number of patients investigated or the diagnostic techniques used. Another potentially important factor is the length of time the patient has snored; a rapidly developing condition secondary to marked weight increase or alcohol intake might not cause so much nervous damage as long-standing habitual snoring.

Some of these studies, notably the new report by Kimoff and coworkers (9), indicate that this neuronal dysfunction may be ameliorated by active OSAS treatment. The question remains as to whether these findings can be replicated in mild sleep apneics or habitual snorers, presently usually not considered candidates for CPAP treatment. Because such patients run a risk of later developing full-blown OSAS, the results in this issue of the Journal might serve as an argument for early preventive treatment.

	References

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