## 4 Discussion
An over-titration of CPAP may have an impact on CSA occurrence: the activation of stretch receptors of the lungs could inhibit the central respiratory output thanks to vagal nerve fibers, leading to the development of a central apnea [18]. Although there is very limited evidence about the use of MAD has also been reported to be associated to the development of TECSA, although only in case reports. In fact, the authors believe that there is little literature on the subject and further studies are necessary to investigate the association between mandibular advancement device and treatment emergent central sleep apnea. [PERSON] et al. have described a case report of a 69-year-old man with OSA and without central apnea at the diagnosis, who refused CPAP because of claustrophobia and accepted MAD as therapy. After three months the patient developed treatment emergent central apnea showing an AHI that was not significantly different from baseline, but 49% of the respiratory events were central. He was monitored for an additional year and then another PSG with his MAD was repeated. The polysomnography showed very mild residual OSA with complete resolution of his central events [17]. [PERSON] et al. have reported two patients with complex sleep apnea after treatment with an oral appliance. Case one was a 59-year-old man who showed severe OSA at polysomnography with severe obstructive sleep apnea and central sleep apnea. He firstly accepted CPAP therapy but subsequently the patient refused it as a treatment option due to claustrophobia and inability to adjust to the mask and chose to pursue an alternative therapy with a mandibular advancement device. The use of MAD resolved obstructive apnea worsening central ones. Case two is a 57-year-old man with a diagnosis of mild OSA who increased the number of central apenas reducing the number of obstructive ones [15] [PERSON] et al. described a case report of a patient of 50-years-old with moderate OSAS who did not reduce obstructive apenas and increased exponentially central apnea during treatment by a bi-bloc MA device. [23] A development of central sleep apnea has also been noted by [PERSON] et al. in a 32-year-old gentleman who initially accepted CPAP as treatment but after few months he refused it describing it too cumbersome to travel with it and then he was advised to an oral device. After 2 months of therapy PSG recorded a higher AHI and a large development of central apenas [40]. [PERSON] et al. described a case of treatment emergent central sleep apnea that had a spontaneous resolution [25]. In conclusion, the results of this research suggest that oral devices are a valid alternative therapy to treat OSA patients, being able to significantly reduce all the altered parameters: AHI, ODI, OSA, CSA and MIXED apnea. In Some isolated cases MAD may contribute, as well as CPAP or surgery, to the development of treatment emergent sleep apnea. However, the current study had several limitations due the limited sample-size of evaluated patients, to the limited observation time and to the lack of homogeneity in the sample group between male and female subjects. However, these data could be used to sample a larger group and to put the findings more in context.