Factors Analysis Related To Fatigue And Daytime Sleepiness In Patients With Myotonic Dystrophy Type Ⅰ

Objective:Fatigue and daytime sleepiness are typical non-muscular symptoms of patients with typeⅠ myotonic dystrophy,and are external manifestations of multiple systemic impairments.In this study,clinical data of 20 patients with typeⅠ tachydystrophy were collected through 2-year follow-up,with the aim of analyzing the factors that may affect the fatigue degree and daytime sleepiness of DM1 patients and the internal correlation between them.To explore the pathogenesis of daytime sleepiness and fatigue in DM1 patients,and describe how fatigue and daytime sleepiness affect the daily life of DM1 patients,so as to provide evidence for the clinical prevention and treatment of DM1.Method:Twenty patients with typeⅠ muscular dystrophy(DM1)who were clinically diagnosed in Bethune First Hospital of Jilin University from January 2016 to January 2019 were screened for inclusion in this study(22 DM1 patients were included at the initial stage of the study,and 20 after two years).Basic information(age,gender,BMI,onset time,duration of disease)of the patients were collected Family information);Clinical symptoms: signs(muscle weakness,myotonia,muscular atrophy,myalgia);Clinical data:serological examination(creatine kinase),imaging(nuclear magnetic resonance of lower limb muscles),electrophysiological examination(multi-system examination of lung function,slit lamp,electrocardiogram),muscle pathological tissue biopsy gene test,etc.The affective state of the patients was also measured by the Hamilton Depression Scale and the Hamilton Anxiety Scale.Muscular Disorder Assessment Scale(MIRS)was also evaluated for 20 DM1 patients in two time periods.And fatigue and Daytime Sleepiness questionnaires,including the Daytime Sleepiness Scale(Daytime Sleepiness Scale;DSS),Fatigue Severity Scale(FSS),followed up 2 years later.This study included two time periods(2016.01-2019.01;T1)and(2018.01 to 2021.01;T2)Cross-sectional study was conducted on the data collected in 2 time periods,followed by longitudinal statistical description and correlation analysis.Result:1.Fatigue and daytime sleepiness scores in DM1 patients were significantly higher than those in FSHD control patients(P<0.01)and healthy control group(P<0.001)17 of 20 patients(90%)met the fatigue criteria and 13 of 20 patients(65%)met the daytime sleepiness criteria;In comparison,only 3 out of 10 patients with FSHD(30%)met fatigue criteria;One normal control group met the criteria for mild daytime sleepiness.No subjects reported fatigue or daytime sleepiness.2.The fatigue degree of DM1 patients was correlated with CTG repeat size of DMPK gene(r= 0.28 P = 0.050)duration of disease(r= 0.38 P= 0.007)degree of muscle pain(r= 0.84 P = 0.001)and forced expiratory volume per second/forced vital capacity FEV1/FVC(r=-0.62,P=0.017).Logistic regression analysis showed that CTG repeat size of DMPK gene was an independent risk factor for fatigue degree of DM1 patients(P =0.004).3.The daytime somnolence symptoms of DM1 patients were significantly different from those of the sexes,and the daytime somnolence was more severe in the female patients(SD:10.5;In male subjects,daytime sleepiness was significantly associated with muscle damage(r=0.96,P=0.001)FEV1/FVC r=0.92,P=0.001).In women,daytime sleepiness was associated with BMI(r=0.32,P=0.036).The degree of fatty muscle(r=0.92,P=0.001)and the state of depression(r=0.73,P=0.03)were significantly correlated with the fatigue degree of all DM1 patients(2patients developed fatigue)at T1-T2(2 years).The higher the frequency of CTG repetition,the longer the course of disease,the more serious the degree of muscle injury,and the higher the change rate of fatigue degree(P <0.05);In addition,there was no correlation between the progression of fatigue and the progression of muscle weakness within2 years.Only 3 DM1 patients experienced an increase in daytime sleepiness during the 2 years.4.The fatigue degree of DM1 patients was correlated with muscle fiber nuclear migration(r=0.305,P=0.039),muscle fiber enzyme deficiency(r=0.451,P= 0.002),and the occurrence rate of broken red fiber(r=0.364,P= 0.013).There was no significant correlation between MIRS score and interstitial hyperplasia(P=0.453)and the occurrence rate of sarcoplasmic mass(P=0.099).5.The degree of nuclear migration in DM1 patients was significantly different between narcolepsy group and non-narcolepsy group(Z=-2.723,P=0.006),and there was statistically significant difference in the rate of broken red fiber between the two groups(Z=-1.977,P=0.0048).The occurrence rate of interstimal hyperplasia was 13 cases in the narcolepsy group and 7 cases in the non-narcolepsy group,and there was no statistically significant difference between the two groups(Z=-0.409,P=0.683).The occurrence rate of sarcoplasm mass was 8 cases in the moderate narcolepsy group and 4 cases in the mild narcolepsy group,and there was no statistically significant difference between the two groups(Z=-1.462,P= 0.144).Conclusions:1.Fatigue and daytime sleepiness are common non-muscular symptoms in patients with type 1 myotonic dystrophy(DM1).It was more common in the face-shoulder-brachial muscular dystrophy group than in the control group with the same degree of disability2.Fatigue degree was significantly correlated with duration of DM1,myalgia degree,FEV1/FVC%,CTG repeat number of DMPK gene and degree of depression.Gender,BMI,degree of fatty muscle,and degree of muscle injury were not related.The CTG duplication number of DMPK gene was an independent risk factor for fatigue.The progression of fatigue over time is not related to the progression of muscle damage.3.In male subjects,daytime sleepiness was associated with FEV1/FVC%and degree of muscle injury,among which FEV1/FVC% was an independent risk factor for daytime sleepiness in DM1 patients.In females,daytime sleepiness was associated with BMI.The degree of fatty muscle was significantly correlated with affective state,and depressive state was an independent risk factor for daytime sleepiness in DM1 female patients.4.The two non-muscular symptoms,fatigue and daytime sleepiness,have a certain basis of skeletal muscle pathological changes.The fatigue degree is correlated with the degree of muscle fiber nuclear migration,the degree of muscle fiber enzyme deficiency,and the occurrence rate of broken red fiber(RRF).The occurrence rate of RRF was an independent predictor of fatigue.The degree of daytime sleepiness was correlated with the degree of muscle fiber nuclear migration,the degree of myofibrase-deficient activity,and the occurrence rate of RRF,among which,the degree of myofibrase-deficient activity was an independent predictor of daytime sleepiness.The presence of sarcoplasmic mass and interstitial hyperplasia was not associated with fatigue or daytime sleepiness.5.Patients with DM1 fatigue and excessive daytime sleepiness symptoms exist significant clinical relevance Daytime sleepiness in patients with high level of fatigue,the subgroup of patients with fatigue degree of daytime sleepiness is also higher.But the degree of progress over a period of time is not parallel.