Assessment Of Prognosis Of Amyotrophic Lateral Sclerosis Based On Quantitative Indicators Of Skeletal Muscle And Subcutaneous Fat On Chest CT

Part I: A Study of Clinical Characteristics and Survival Status of 64 Patients with Amyotrophic Lateral Sclerosis Objective: To analyze the relationship between clinical characteristics,disease stage and survival status of patients with sporadic amyotrophic lateral sclerosis(ALS).Methods: The clinical data of patients with sporadic ALS admitted from January 2017 to August 2021 at the Affiliated Hospital of Southeast University were retrospectively collected,64 cases were identified by nadir criteria,and survival status was determined by follow-up.The groups were grouped by gender,site of onset,and disease stage,and differences between groups were analyzed using parametric and nonparametric tests.One-factor survival analysis was performed on the results of clinical characteristics,and a COX regression model was established based on the results of the one-factor survival analysis.Results:1.Only height(p<0.001)differed significantly between genders of ALS patients,while age,disease duration,delay in diagnosis,body mass index(BMI),site of disease onset,King’s Clinical Staging(KCS),Modified ALS Functional Rating Scale(ALSFRS-R),ALS Baseline Respiratory Function Score(ALSFRS-R-R)and baseline disease progression rate(DPR)were not different.A total of 2 patients were lost to follow-up,with an overall loss rate of 3.13%.2.Age(OR=1.07,95% CI [1.01,1.13],p=0.031)and DPR(OR=3.31,95% CI [1.51,7.26],p=0.003)were greater in the Amyotrophic Lateral Sclerosis Patient with LimbOnset(L-ALS)than in the Amyotrophic Lateral Sclerosis Patient with Bulbar-Onset(B-ALS).The ALSFRS-R(OR=0.79,95% CI [0.69,0.91],p=0.001)and ALSFRS-RR(OR=0.46,95% CI [0.30,0.71],p<0.001)were smaller in the B-ALS than in the LALS.3.ALSFRS-R(p<0.001),ALSFRS-R-R(p<0.001),DPR(p<0.001)and follow-up survival status were significantly different between different KCS stages in ALS patients.4.Univariate survival analysis suggested significant differences between groups with different sites of onset(p<0.001)and KCS stage(p<0.001);patient’s disease duration(OR=1.078,95% CI [1.026,1.146],p=0.006)and time to diagnosis delay(OR=0.825,95% CI [0.699,0.931],p = 0.007)were able to increase the risk of death in ALS patients.5.COX regression suggested the duration of disease(HR=1.039,95% CI [1.004,1.075],p=0.03)and KCS stage(KCS stage 3 HR=13.704,95% CI [1.636,114.767],p=0.016)in ALS patients as independent risk factors.Conclusion:1.B-ALS is associated with lower ALS functional scores,lower respiratory-related ALS functional scores,faster progression rates and higher mortality than L-ALS.2.As KCS staging progressed,ALS functional scores and respiratory-related ALS functional scores decreased,the rate of disease progression accelerated and the outcome event of tracheal intubation/death occurred increased.3.KCS stage and disease duration are closely related to survival prognosis of ALS patients,with longer disease duration and relatively advanced KCS having a high risk of death.Part II Assessment of Amyotrophic Lateral Sclerosis Prognosis Based on Image J Quantitative Chest CT of Skeletal Muscle and Subcutaneous FatObjective: To quantitatively analyze the skeletal muscle cross-sectional area(SMA),skeletal muscle density(SMD),paravertebral muscle area(PMA),paravertebral muscle density(PMD),subcutaneous fat area(SFA),and subcutaneous fat density(SFD)at the first lumbar level(L1)within chest CT in patients with amyotrophic lateral sclerosis(ALS),and to study their relationship with different diagnostic staging,clinical staging,disease severity,and The relationship between PMD,SFA,and SFD and different diagnostic staging,clinical stage,disease severity and survival prognosis of ALS was investigated.Methods: A single cohort observational study was used to calculate baseline disease progression rate(DPR)and survival by applying clinical data,chest CT imaging data from the first part of the ALS patient cohort,and regular follow-up of patients’ revised ALS functional status score(ALSFRS-R)and survival.L1 SMA,L1 SMD,L1 PMA,L1 PMD,L1 SFA,and L1 SFD were analyzed in relation to gender,site of onset,and King’s clinical staging(KCS)in ALS patients.Correlation analysis of quantitative chest CT with ALSFRS-R and ALS baseline respiratory function score(ALSFRS-R-R)in ALS patients was performed.Quantitative analysis and comparison of the variability of baseline and follow-up chest CT.Kaplan-Meier survival curves were plotted by log-rank test based on follow-up outcomes for the two groups with quantitative levels of high and low level of chest CT.A Cox proportional risk regression model was constructed to assess the relationship between muscle fat quantification results and survival of ALS patients based on the results of the univariate survival analysis.Results:1.The percentage of ALS patients with skeletal muscle reduction status was 78.13%,with a total of 38 male patients(86.36%)and 12 female patients(60.00%).The L1SMA(OR=1.19,95% CI [1.05,1.34],p<0.001),L1 SMI(OR=4.22,95%CI[1.22,14.61],p=0.023)and L1 PMA(OR=1.13,95% CI [1.03,1.22],p<0.001)were significantly higher in male patients than in female patients;L1 SFA(OR=0.95,95%CI [0.92,0.98],p<0.001)was significantly lower in male patients than in female patients.2.L1 SMD(OR=4.06,95% CI [1.23,13.33],p=0.02),L1 PMA(1.07,95% CI [1.001,1.139],p=0.046)and L1PMD(OR=1.08,95% CI [1.01,1.15],p p=0.02)were significantly higher than in ALS patients with medullary onset(B-ALS);while L1SFD(OR=0.91,95 CI [0.85,0.98],p=0.01)was significantly lower than in B-ALS.3.L1 SMA(p=0.011),L1 PMA(p=0.026),and L1 PMD(p=0.009)were significantly different among different KCS stages;L1 SMI was only significantly different between stage 1 and 2 of KCS(p=0.018);L1 SFD was significantly different between stage 1 and 3 of KCS(p=0.029),stage 2 and 3 of KCS There was a significant difference between KCS stage 1 and 3(p=0.029),KCS stage 2 and 3(p=0.022).4.There was no correlation between ALSFRS-R score,ALSFRS-R-R score and quantitative indexes of chest CT.5.There were significant differences in quantitative chest CT indexes L1 SMA(p<0.001),L1 PMA(p<0.001),L1 SMD(p=0.02),L1PMD(p=0.04),L1 SFD(p=0.003),and L1 SMI(p<0.001)between the baseline group and the group with follow-up.6.The ROC curve using survival outcome as an indicator yielded KCS stage(AUC=0.93)as a high predictor of poor survival outcome,while neither the rate of change in quantitative chest CT nor the rate of disease progression after follow-up(FDPR)was sensitive to the prediction of poor survival outcome in patients.ROC curves using KCS stage 3 as an outcome indicator yielded L1 SMI rate of change(AUC=0.85),L1 SFD rate of change(AUC=0.69),L1 PMD rate of change(AUC=0.67),and L1 SFA rate of change(AUC=0.65)were highly sensitive for predicting KCS stage 3,while post-follow-up disease progression rate(FDPR)and the remaining chest CT rate of change indicators were not sensitive to the prediction of KCS stage.7.The survival rate was higher in the high level L1 SMA group compared to the low level L1 SMA group(p=0.038);the survival rate was higher in the high level L1 SMI group compared to the low level L1 SMI group(p=0.01),and the survival rate was higher in the high level L1 PMD group compared to the low level L1 PMD group(p=0.0044).There was no difference in the survival rates of L1 SMD,L1 PMA,L1 SFA and L1 SFD between the high-and low-level groups.8.The COX proportional risk regression model suggested that L1 SMA(HR=0.97,95% CI [0.943,0.997],p=0.032)and L1 SMI(HR=0.92,95% CI [0.848,0.996],p=0.04)were independent risk factors for survival in ALS patients.The Cox proportional risk regression model C-index for L1 SMA and L1 SMI combined with disease duration,KCS stage,and delay in diagnosis was 0.858(0.786,0.929).Conclusion:1.The presence of skeletal muscle reduction status was prevalent in ALS population with 78.13%.Differences in local muscle fat cross-sectional area existed among ALS patients of different genders,while there were no differences in muscle density and fat density.2.ALS patients with medullary onset already had poor paravertebral muscle status and higher density subcutaneous fat status at the time of initial diagnosis.3.As disease staging progresses,ALS patients have progression of total muscle area,paravertebral muscle area and density,and subcutaneous fat density at a single level.4.Changes in follow-up chest CT can be sensitive to the progression of disease staging in ALS.5.Higher skeletal muscle mass suggests a relatively better survival outcome.L1 SMA and L1 SMI are protective factors for survival in ALS patients,and an increase in L1 SMA or L1 SMI reduces the risk of death/tracheal intubation by 3% and 8%,respectively.Part III Correlation between Skeletal Muscle Index and Blood Creatinine,Glycosylated Haemoglobin and Lipids in ALS PatientsObjective: To investigate the relationship between the first lumbar skeletal muscle index(L1 SMI)and hematological indices of nutritional status including glycated hemoglobin(Hb A1c),triglycerides(TG),high-density lipoprotein(HDL),low-density lipoprotein(LDL)and serum creatinine(SCr)in patients with amyotrophic lateral sclerosis(ALS).Methods: The relationship between L1 SMI and HbA1 c,TG,LDL,HDL,and SCr was analyzed using a single cohort observational study method,applying clinical data and chest CT imaging data from the first part of the ALS patient cohort.Results:1.There were significant differences between low level L1 SMI and normal L1 SMI group sex(p=0.018),SCr(p=0.036),HDL(p=0.009).2.There was a significant difference in blood TG levels(p=0.006)in patients with primary ALS with different sites of onset.3.There was no significant difference in hematological indicators of nutritional status among different King’s clinical stages(KCS).4.Univariate linear correlation analysis suggested a positive correlation between SCr and L1 SMI in patients with limb-initiating ALS(L-ALS)(r=0.36,p=0.005);HDL was negatively correlated with L1 SMI in L-ALS(r=-0.28,p=0.03).5.After adjusting the site of onset,age,and gender as covariates,a linear regression model linear regression suggested that SCr(β=0.145,p=0.005)and HDL(β=-6.95,p=0.022)were still correlated with L1 SMI.6.There was no correlation between each hematological index and revised ALS functional status score(ALSFRS-R),ALS baseline respiratory function score(ALSFRS-R-R),and baseline disease progression rate(DPR).7.Multifactorial analysis of L1 SMI reduction suggested Scr(OR=1.04,95% CI [1.0,1.08],p=0.04)as a protective factor.HDL(OR=0.05,95% CI [0.0,0.43],p=0.01)was a risk factor;patients’ ALSFRS-R score,ALSFRS-R-R score,age,and site of onset did not have a significant effect on L1 SMI.Conclusion:The reduction of skeletal muscle mass in ALS patients is associated with creatinine and HDL;creatinine and HDL can reflect skeletal muscle changes in patients with limb initiation type;creatinine is a protective factor for muscle loss in ALS patients;HDL is a risk factor for muscle loss in ALS patients.