| Objective:Part 1:To observe the changes of nocturnal sleep architecture in patients with amyotrophic lateral sclerosis(ALS),and to explore the factors that influence the sleep architecture of ALS.Part 2:To investigate the incidence,manifestations,correlation factors and its clinical value of sleep disordered breathing(SDB)at an early stage of ALS.Part 3:We examined the features of SDB in patients with early stage ALS to assess whether SDB is a useful predictor of respiratory function decline.Methods:Part 1:Participants according to the diagnostic criteria of ALS patients at an early stage(research group)and healthy subjects(control group)were examined by PSG to assess the conditions of night breathing and changes of sleep structure.Recordings were collected,such as total recorded time(TRT),total sleep time(TST),sleep latency(SL),sleep efficiency(SE),apperception time(AT),wake after sleep onset(WASO),phase S1,S2,S3,and REM sleep.We also analyzed co-related factors in sleep progress and sleep architecture of ALS patients.Part 2:The PSG data of participants in Part 1 were analyzed,the AHI index of each patient was calculated,the incidence of SDB in the two groups was compared,and co-related factors affecting SDB were statistical regression analyzed.Part 3:We used respiratory function tests and blood gas analyses to identify early stage ALS.Participants with normal daytime respiratory function and arterial blood gas levels underwent polysomnography(PSG).The patients were divided into the SDB and non-SDB groups based on the apnea and hypopnea index(AHI)results,and followed them for 1 year to discover differences in the incidence of respiratory symptoms between groups.Results:69 cases of ALS patients(research group)at an early stage were enrolled during the observation period,which included 48 males and 21 females,age(31~72 y),average(49.35±6.74),body mass index(BMI)16.12~24.88kg/m~2,average(20.33±2.67)kg/m~2,and the course of disease(DD)2~48months,average(18.2±13.5)months,ALSFRS-R 37~46,average(21 months).69 healthy subjects(control group)were enrolled to undergo PSG,including 47 men,22 women,age(35~70)years,average age(53.45±7.54)y,BMI(16.76~23.62)kg/m~2,with an average of(20.82±1.69)kg/m~2.Part 1:Total sleep time(TST)、sleep efficiency(SE)in the experimental group was significantly decreased,wake after sleep onset(WASO)was significantly prolonged,S2 phase sleep,s3 phase sleep and rapid eye movement sleep in the experimental group was obviously decreased compared with the control group.(1)Total sleep time(TST)in the experimental group was significantly shorter than in the matched group(P<0.001),sleep efficiency(SE)was significantly decreased(P<0.001),wake after sleep onset(WASO)was significantly prolonged(P<0.001);Compared with the control group,awaking time(AT)and sleep latency(SL)in the experimental group was not significant different(P>0.05).(2)S2 phase sleep,s3 phase sleep and rapid eye movement sleep in the experimental group was obviously decreased(P<0.001,P<0.001,P<0.05),compared with the control group;No significant difference between the two group was in the Stage 1 sleep(P>0.05).(3)The TST in the experimental group was negatively correlated with age(r=-0.279,P>0.05),and the lowest SpO2 was positively correlated with TST(r=0.314,P<0.05).There was no significant correlation between TST and duration of disease,total score of BMI,ALSFRS-R,AHI and average SpO2(P>0.05).(4)The age,BMI,duration of the disease,the total AHI,mean SpO2,minSpO2,and ALSFRS-R scores in the experimental group showed no linear correlation with SL,SE,and AT(P>0.05).(5)WASO in the experimental group was positively correlated with age(r=0.368,P<0.05).(6)The linear regression analysis of factors that may affect S1 and S3 sleep in the experimental group showed that there was no significant correlation between S1 phase sleep,S3 phase sleep with age,BMI,course of disease,ALSFRS-R score,total AHI,mean SpO2,min SpO2.(7)Linear regression analysis was carried out on the factors that may affect S2 phase sleep in the experimental group,suggesting that S2 phase sleep was negatively correlated with the course of sleep(r=-0.359,P<0.05),S2 phase sleep was positively correlated with ALSFRS-R score and min SpO2(P<0.05).(8)The age in the experimental group was negatively correlated with REM(r=-0.561,P<0.001),the other factors had no linear regression relationship with REM(P>0.05).Part 2:68.12%patients in the research group had an AHI of more than 5 times per hour.Many factors can affect on sleep disorders in early ALS patients.(1)In our research,we found out that 47 of the 69(68.11%)participants had SDB.Compared with the experimental group,total apnea hypopnea index(AHI)、rapid eye movement AHI,non-rapid eye movement AHI,obstructive and mixed AHI were significant higher(P<0.01),average SpO2 and minimum SpO2 in the experimental group were significant lower(P<0.001 and P<0.05),central AHI have no significant higher(P>0.05).(2)Due to the analysis of the related factors affecting the average SpO2 in the experimental group,it was found that the average SpO2 was negatively correlated with BMI and whether bulbar involvement(rs=-0.428,P<0.05and rs=-0.487,P<0.05),suggesting that the higher BMI in ALS patients,the lower the average SpO2.In ALS patients,the average SpO2 was lower than those without medullary paralysis;Mean SpO2 was positively correlated with the ALSFRS-R score(rs=0.531,P<0.05),suggesting that the more serious the symptoms of the ALS patients,the lower the Mean SpO2.(3)Regression analysis was carried out on the correlation factors of the lowest SpO2 in the experimental group.The results did not find the linear correlation between the lowest Sp O2 and the course of disease,age,BMI,ALSFRS-R score,FVC,and the medulla oblongata(P>0.05).(4)Regression analysis of factors that may affect the total AHI indicated that the patients’age,the course of ALS,BMI,ALSFRS-R,FVC,whether bulbar involvement had no linear regression relationship with total AHI(P>0.05).Part 3:The incidence of dyspnea in early ALS patients with SDB is significantly higher than that of ALS patients without SDB,which suggests that SDB can be used to predict the early decline of respiratory function in patients with ALS.(1)In total,69 patients with ALS were collected during the observation period,39 of whom had normal daytime respiratory function and arterial blood gas levels.Of these,38 agreed to undergo PSG.The patients were divided into the SDB group(17cases)and non-SDB group(21 cases)based on the apnea and hypopnea index(AHI)results.There was no significant difference in TSP,total sleep time,sleep efficiency,sleep latency and mean SpO2 between the two groups.(2)The 38 patients who underwent PSG were followed up regularly for 1 year,and no patients was lost during the follow-up period.Nine of the 17 patients in the SDB group developed respiratory dysfunction symptoms,and two of them died(one died of pulmonary infection and the other of sudden death).Four of the 23 patients in the non-SDB group developed dyspnea,none of these patients died.The incidence of respiratory symptoms was significantly higher in the SDB group than it was in the non-SDB group(risk ratio:2.97,95%confidence interval:1.30-6.76).(3)The remaining participants with abnormal daytime pulmonary function were 30 cases,of which 29 cases had an AHI of more than 5 times/hours,11 cases with an AHI of more than 10 times per hour.At the same time,the patients with abnormal lung function were followed up for 1 years.The results showed that all the 30 cases had different types of respiratory insufficiency,8 of them died,6 of which died of pulmonary infection.Conclusion:(1)The ALS patients at an early stage may have obvious changes in sleep architecture,age,duration of disease and severity of the disease are important factors affecting the sleep architecture changes of ALS patients.(2)ALS patients at the early stage may have various types of SDB,of which nocturnal hypoventilation and OSA are the most common.Whether bulbar involvement,ALSFRS-R,BMI,FVC are important factors affecting ALS patients with SDB.ALS patients with normal daytime lung function may already suffered SDB.(3)Sleep disordered breathing may already occur in the early stage of ALS patients with normal daytime lung function,and PSG is better in the assessment of respiratory function of ALS patients. |