Furthermore an independent association between

Furthermore, an independent association between SOS episodes and sleep disturbances such as RBD symptoms was observed. Cumulative evidence shows that RBD precedes the development of PD by many years [24–26]. Previously, a reduction of median cerebellar peduncle that carries key structures from the reticular ascending activating system has been associated with EDS in PD patients [27]. These facts indicate that brain structure abnormalities are on the basis of RBD and SOS in PD. Controversy remains over the role of sleep farnesoid x receptor in EDS and SOS episodes in PD. Previously, a study has shown that snoring, an indicator of sleep apnea, was the only factor associated with EDS in PD [28]. Recently, CPAP therapy improved daytime sleepiness in patients with PD [29]. Importantly, it is essential to examine factors influencing not only EDS but also the more severe SOS episodes. Potentially, SOS episodes are more threatening and according to our data, they are more related to disease duration and sleep disturbances. Another important issue is to investigate about the presence of RBD that not only contribute for EDS and SOS episodes but is closely related to the presence of sleep apnea. All these issues are important to consider in future attempts to modify EDS and SOS episodes in PD patients. For instance, the effects of reducing overnight immobility and discomfort on vigilance and daytime performance remain to be tested. To date, no evidence has shown that increasing sleep quantity and quality ameliorate EDS or SOS episodes in PD. In this study, medication did not influence the severity of EDS or the presence of SOS episodes. It is largely recognized that dopamine agonists can precipitate these somewhat narcoleptic events or “sleep attacks” in PD patients [30,31]. The effects of dopamine agonists on sleep have been variable and possibly related to the severity of baseline symptoms [32]. Improvement of sleep symptoms and fatigue have been reported after the use of dopamine agonists [33]. Ropinirole and other non-ergot dopamine D2 receptor agonists cause selective loss of orexin-immunoreactive neurons in culture of rat hypothalamus [34]. An explanation for these findings may be a D2 receptor-mediated presynaptic suppression of glutamatergic excitatory inputs to orexin neurons causing silencing of excitatory activity of orexin neurons and secondary depletion of orexin. This unwanted dopamine agonist effect would further complicate the orexin loss that occurs with PD neurodegeneration [35]. All this evidence not only confirms a disturbance of the orexinergic system and secondary sleep/arousal cycle disruption but also shows a great deal of clinical variability among patients. It is reasonable to consider that EDS and/or SOS are not influenced only by the use of dopaminergic agonists but by the disease process and the several associated cerebral alterations that occur in PD [36,37]. Limitations to this study must be acknowledged. The present data are based on the evaluation of a reduced number of patients. However, the frequency of EDS and SOS episodes are in agreement with a study involving a large number of individuals [8]. Also, this study is based on questionnaires and objective evidence obtained from polysomnography and multiple sleep latency tests would be of interest. Of note, studies about the value of subjective measures of sleepiness have led to the idea that objective and subjective measures have different meaning [38,39]. Furthermore, an association between subjective sleep quality and sleep measures obtained from polysomnography has not been previously found [40]. It has been said that total dopaminergic drug dose rather than the specific dopamine agonist used is the best predictor of daytime sleepiness in PD patients receiving dopamine agonist therapy [41].
Acknowledgments This study was partially supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).