| Part 1 Background and Objective:Progressive supranuclear palsy(PSP)is an adult-onset,rapidly progressive neurodegenerative disorder with a poor prognosis due to its poor response to medications and lack of effective treatments.In 2017,the International Movement Disorders Society(MDS)published new diagnostic criteria for PSP that redefine multiple clinical subtypes.It significantly improved the diagnostic sensitivity and provided an opportunity for further research on PSP.Previous studies have shown that approximately 60% of PSP patients develop varying degrees of sleep disorders,including insomnia,rapid eye movement sleep behavior disorder(RBD),restless legs syndrome(RLS),and excessive daytime sleepiness,which severely affect patients’ quality of life.At present,only a few clinical studies with small samples have been published internationally,and the results of different studies vary and are controversial.There are also no published studies on this topic in Chinese population.To fill the research gap,we conducted a cross-sectional survey by means of clinical field questionnaire to understand the incidence,basic characteristics and relevant influencing factors of various types of sleep disorders in PSP based on a relatively large sample in southwest China,and explored the possible mechanisms of their occurrence and impact on patients’ quality of life.Materials and Methods:From January 2019 to January 2021,we consecutively included patients with PSP who met the MDS diagnostic criteria and fit the prior-defined exclusion and inclusion criteria.These patients were seen in the outpatient and inpatient wards of the Department of Neurology,West China Hospital,Sichuan University.Basic demographics of the population and relevant clinical history were collected,followed by scale assessment.Patients were divided into poor sleep quality group and good sleep quality group with a cut-off value of PSQI≥6;patients were divided into RBD group and non-RBD group with a cut-off value of RBD-HK≥19;patients were divided into excessive daytime sleepiness group and non-excessive daytime sleepiness group with a cut-off value of ESS≥10;and patients were divided into RLS group and non-RLS group with the presence or absence of RLS.Comparisons between groups and correlation analysis were performed using IBM SPSS Statistics 25.0 software and two-sided P≤0.05 was considered statistically significant.Results: A total of 153 patients were finally included,with a median age of 68(61~73)years,a mean age of onset at 63.7±9.3 years,and a median disease duration of 2(1~4)years,61.4% were men.78.4%(120/153)of patients had at least one sleep disorder:1.The prevalence of poor sleep quality among PSP patients was 67.3%(103/150).Comparison of clinical data and demographic characteristics showed that patients with poor sleep quality were less educated(high school and above: 27.2% vs 46%,P=0.021)and used hypnotic drugs more often(18.4% vs 2%,P=0.005).Scale assessments showed that the poor sleep quality group was more ill [PSPRS total score: 24(19~34)vs 21.5(17~28),P=0.011],and had more significant non-motor symptoms [NMSS score: 46(30~68)vs 23(13.75~40),P<0.001], anxiety [HAMA score: 10(6~15.25)vs 6(3.75~9),P < 0.001],depression [HAMD-24 score: 12(6~17)vs 6(4~11),P < 0.001],excessive daytime sleepiness [ESS score: 6(3~10)vs 2(0.75~5),P < 0.001] and fatigue [FSS mean score: 3.44(1.00~5.67)vs 1.22(1.00~3.64),P=0.003].This condition impacted the quality of life [PDQ-39 score: 30(17~48)vs 18(10~31.5),P=0.012].Multifactorial analysis showed that non-motor symptoms and anxiety were associated risk factors for poor sleep quality: OR=1.022,95% CI 1.004 to 1.041,P=0.016;OR=1.079,95% CI 1.003 to 1.161,P=0.042.2.The prevalence of RLS among PSP patients was 4.6%(7/153).There were no statistical differences in clinical data and demographic characteristics between the RLS and non-RLS groups.Scale assessment showed that RLS affected patients’ quality of life [PDQ-39 score: 35(33~60)vs 23.5(13.75~46),P=0.039].The results of multifactorial analysis showed that disease severity may be associated with the occurrence of RLS: OR=1.052,95% CI 1.014 to 1.091,P=0.007.3.The prevalence of RBD among PSP patients was 28.1%(43/153).Comparison of clinical data and demographic characteristics showed that patients with RBD had more frequent constipation(62.8% vs 36.4%,P=0.003),decreased sense of smell(34.9% vs 19.1%,P=0.038)and lower alcohol consumption(7% vs 32.7%,P=0.001).The results of the scale assessment showed more significant cognitive impairment [MMSE score: 26(24~28)vs 27(24~29),P=0.049] and fatigue [FSS mean score: 3.78(1.00~5.89)vs 1.67(1.00~4.69),P=0.027] in the RBD group.Results of multifactorial analysis showed that alcohol consumption and constipation were associated factors: OR=0.160,95% CI 0.046 to 0.562,P=0.004;OR=2.839,95% CI 1.333 to 6.044,P=0.007.4.The prevalence of excessive daytime sleepiness in PSP patients was 22.9%(35/153).Comparison of clinical data and demographic characteristics showed that P=0.005)and were older [72(66~75)vs 66.5(59~72),P=0.004].Scale assessments showed that patients with excessive daytime sleepiness were sicker [PSPRS total score: 28(23~42)vs 22(18~29.25),P=0.008],had more significant non-motor symptoms [NMSS score: 65(44~79)vs 35.5(17.75~52),P<0.001],cognitive impairment [MMSE score: 26(23~28)vs 27(24~29),P=0.048],anxiety [HAMA score: 12(8~18)vs 8(4~12.5),P=0.009],depression [HAMD-24 score: 13(6~17)vs 8(5~14),P=0.031],fatigue [FSS mean score: 4.11(1.56~6.00)vs 1.67(1.00~4.53),P=0.002] and poor sleep [PSQI score: 11(8~12)vs 7(3.75~10),P=0.002].This condition affected patients’ quality of life [PDQ-39 score: 38(21~64)vs 21.5(12~41.25),P=0.001].Multifactorial analysis showed that age and non-motor symptoms were possible risk factors: OR=1.074,95% CI 1.016 to 1.135,P=0.011;OR=1.030,95% CI 1.014 to 1.045,P<0.001.Conclusion: PSP patients have prominent sleep disturbances(poor sleep quality,RLS,RBD,and excessive daytime sleepiness),and all types of sleep disorders interact with a range of motor and non-motor symptoms to severely affect the patients’ quality of life.Clinicians need to pay attention to these disorders and achieve early patient recognition and management.Part 2 Background and Objective:Polysomnography(PSG)is a procedure that utilizes electroencephalogram,electro-oculogram,electromyogram,electrocardiogram,and pulse oximetry,as well as airflow and respiratory effort,to evaluate for underlying causes of sleep disturbances and is considered the gold standard for diagnosing sleep disorders.Previous studies have shown that PSP patients are prone to altered sleep architecture,obstructive sleep apnea(OSA),rapid eye movement sleep behavior disorder(RBD),and periodic limb movement during sleep(PLMS).However,there are large controversies due to the small sample sizes and use of inconsistent methodology and diagnostic criteria across different studies.There are ethnic and cultural differences in sleep disorders,however,no relevant studies have been conducted in China.Given the above reasons,in this part we proposed to conduct a cross-sectional study by means of one overnight PSG in order to objectively understand the incidence,basic characteristics and related factors of various sleep disorders in PSP in southwest China,and to explore their correlations.Materials and Methods:After completing the clinical scale assessment in part 1,the patients were told about the relevance of sleep disorders to their disease,and they voluntarily chose whether to undergo a PSG,and if cooperated,they were included in this part of the study.Sex-and age-matched individuals without previous neuropsychiatric disorders were selected as controls.The enrolled population underwent one overnight PSG according to standard operating protocols,with OSA diagnosed when AHI≥10/h and PLMS diagnosed when PLMI>15/h,while RBD was diagnosed based on PSG-confirmed REM-sleep without atonia + clinical dream enactment behaviors.All data analyses were performed in IBM SPSS Statistics 25.0 software and were considered statistically significant at a two-sided P≤0.05.Results: A total of 86 PSP cases were finally included,as well as 24 healthy controls.The median age of PSP patients was 68(62.75~73)years,and 55.8%(48/86)were male,which were not statistically different from controls.In this part,91.9%(79/86)cases had at least one sleep disorder.1.Compared with healthy controls,in terms of sleep duration,total sleep time,N2,N3,REM and NREM sleep duration were significantly reduced in PSP,while N1 sleep duration was prolonged and sleep efficiency was reduced;in terms of sleep percentage,PSP had increased N1 sleep percentage,while almost no N3 sleep,and the rest were not significantly different;in terms of sleep-related event index,PSP had lower microarousal index,higher apnea hypopnea index and increased OSA incidence,while mean blood oxygen and minimum blood oxygen saturation were significantly lower,and all these differences were statistically significant.2.PLMS was not found in the included PSP population and could not be further analyzed.3.The prevalence of PSP with RBD was 27.9%(24/86).In terms of clinical and demographic characteristics,the RBD group was more likely to have a history of constipation(66.7% vs 38.7%,P=0.020);in sleep-related indicators,there was no significant difference between the RBD and non-RBD groups;in terms of scale scores,the RBD group had more severe non-motor symptoms [NMSS score: 53(34.75~73)vs 36(18.75~49),P=0.016],poorer quality of life [PDQ-39 score: 34.5(21.5~53)vs 19(11.5~40.25),P=0.020],and more pronounced fatigue symptoms [FSS mean score: 3.72(1.06~6.22)vs 1.44(1.00~4.25),P=0.042].Multifactorial logistic regression analysis showed that constipation was a possible risk factor for PSP with RBD: OR=3.167,95% CI 1.176 to 8.528,P=0.023.4.The prevalence of OSA in PSP was 59.3%(51/86).In terms of clinical and demographic characteristics,the OSA group was older [70(66~74)vs 65(57~69),P=0.003] and had a later age of onset [67(61.75~72)vs 62(54.7~67.5),P=0.007];in terms of sleep-related indicators,the OSA group had a longer and higher proportion of N1 sleep,a decreased proportion of N2 sleep,and an increased duration of NREM sleep,along with an increase in microarousal index,apnea hypopnea index and oxygen desaturation index,and a decrease in mean blood oxygen and minimum blood oxygen saturation,all of which were statistically significant;in terms of scale scores,the OSA group had worse quality of life [PDQ-39 score: 29(17~54)vs 18(9~30),P=0.012],more significant cognitive impairment [MMSE score: 26(24~28)vs 28(25~30),P=0.036],and more significant daytime sleepiness and fatigue symptoms [ESS score: 6(3~9)vs 3(1~6),P=0.025;FSS mean score: 3.11(1.00~5.89)vs 1.00(1.00~3.22),P=0.009].Multifactorial logistic regression analysis showed that advanced age was an independent risk factor for the development of OSA: OR=1.059,95% CI 1.008 to 1.112,P=0.024.5.The prevalence of PSP with excessive daytime sleepiness was 17.4%(15/86),and the prevalence of PSP with poor sleep quality was 65.1%(56/86).Mean blood oxygen was reduced in the daytime hypersomnolence group compared to the non-daytime hypersomnolence group,while there were no significant differences in other sleep-related indicators.There were no statistically significant differences in sleep-related indicators between the PSP with and without poor sleep quality groups.After adjusting for age,sex,BMI and disease severity PSPRS scores,excessive daytime sleepiness and poor sleep quality were not significantly associated with sleep-related events.Conclusion: The results in this part further confirmed the presence of various sleep disorders(altered sleep architecture,OSA,RBD,excessive daytime sleepiness and poor sleep quality)in PSP.Because of the high incidence of OSA,clinicians should enhance patient screening and appropriately arrange PSG to aid the diagnosis,eventually to achieve timely intervention and improve patients’ quality of life. |
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