Drainage Function Of Meningeal Lymphatic Vessels In Patients With Parkinson’s Disease

BackgroundParkinson’s disease(PD)is a common neurodegenerative disease.Its main clinical manifestations include motor symptoms such as static tremor,bradykinesia,myotonia and postural balance disorder,and may be accompanied by non-motor symptoms such as olfactory dysfunction,sleep disturbance,autonomic nervous dysfunction,cognitive and mental disorders.PD,MSA(Multiple system atrophy,MSA),DLB(Dementia with Lewy bodies,DLB)all belong to alpha synuclein(a-syn)diseases,pathologic features are misfolding a-syn positive inclusions sedimentary in neurons or glial cells,nerve fibers,and spread along the axons in the Central nervous system(Central nervous system,CNS).The clearance of α-syn positive inclusions in CNS has become a major target for the attack of PD.However,until now,the treatment of PD,including drugs or surgery,can only improve the clinical symptoms of patients,not prevent the development of the disease itself,let alone cure it.In 2015,the meningeal lymphatic vessels(mLVs)were first discovered as a tubular structure surrounding superior sagittal sinus(SSS)on the dorsal side of the brain and sigmoid sinus(SS)on the basilar,known as mLVs-SSS(left-mLVs-SSS,right-mLVs-SSS,lower-mLVs-SSS)and mLVs-SS(left-mLVs-SS,right-mLVs-SS,lower-mLVs-SS)respectively.This finding overturns the basic hypothesis of neuroimmunology.Studies have confirmed that the mLVs is an important pathway for the removal of metabolites and abnormal macromolecules of brain tissue.Up to now,animal studies have confirmed that mLVs dysfunction is associated with the pathogenesis of some neurodegenerative diseases,such as PD and Alzheimer’s disease(AD),but there is no direct evidence to confirm the association between human mLVs function and PD.In view of the above research basis,this study aims to evaluate and compare the drainage function of PD patients with Atypical Parkinsonian(AP)patients and healthy controls(NC)by using Dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)technique.At the same time,the correlation between the changes in drainage function of mLVs and the severity of PD patients were analyzed,so as to explore the role of mLVs in the occurrence and development of PD and provide a new method for the diagnosis of PD,and find a new breakthrough for the clearance of α-syn positive inclusion bodies.ObjectiveDCE-MRI was performed to assess the drainage function of mLVs-SSS and mLVs-SS in PD,MSA,Progressive Supranuclear Palsy-Richardson Syndrome(PSP-RS)and NC.To explore the role of drainage function of mLVs in the occurrence and development of PD and the value of DCE-MRI in the differential diagnosis of PD.Methods1.From sep 2018 to sep 2020,166 PD patients,98 patients with MSA,96 patients with PSP-RS,162 NC were enrolled in the Department of Neurology of the first affiliated hospital of Zhengzhou University.After rigorous screening process,156 PD patients,92 patients with MSA,90 patients with PSP-RS,152 NC were in the group.Collected the clinical data of all the subjects,including gender,age,course of the disease,a daily dose of levodopa dosage,H&Y classification,and UPDRS Ⅲscores of PD patients,UMSARS Ⅱ scores of MSA patients,PSP Ⅳ-Ⅵ scores of PSP-RS patients.All the participants’ MMSE scores,time up and go test scores,tandem gait test scores were also be collected.Statistical analysis of these clinical baseline information were performed;2.The time-intensity curve(TIC)of mLVs-SSS(left-mLVs-SSS,right-mLVs-SSS,lower-mLVs-SSS)or mLVs-SS(left-mLVs-SS,right-mLVs-SS,lower-mLVs-SS)in PD,MSA,PSP-RS patients and NC were obtained by DCE-MRI.DCE-MRI parameters were obtained by TIC,the parameters including Time to peak(TTP),Wash in rate,Area under the curve(AUC).Mean DCE-MRI parameters of left-mLVs-SSS,right-mLVs-SSS,lower-mLVs-SSS or left-mLVs-SS,right-mLVs-SS,lower-mLVs-SS were taken respectively,and the average parameter values of mLVs-SSS or mLVs-SS of the four groups of subjects were compared.Thus,the drainage function of PD,MSA,PSP-RS patients and NC mLVs-SSS and mLVs-SS were quantitatively evaluated;3.The correlation between mLVs-SSS or mLVs-SS DCE-MRI parameters and H&Y classification in PD patients were analyzed,so as to explore the correlation between the drainage function of mLVs and the severity of PD;4.The ROC curves were used to explore the sensitivity and specificity of DCE-MRI parameters for the differentiation of PD and AP;5.The vital signs,including blood pressure,heart rate and average flow velocity and vessel diameter of internal carotid artery(ICA)and external carotid artery(ECA),before and after DCE-MRI examination of the four groups of subjects were collected in order to exclude the effect of hemodynamics on mLVs drainage function;6.After the DCE-MRI(about 25min after gadolinium injection),all subjects underwent the high-resolution MRI sequence scanning of mLVs.The mean cross-sectional area of mLVs-SSS or mLVs-SS of the four groups of subjects were collected and compared to exclude the influence of cross-sectional area of mLVs on the drainage function of mLVs.Results1.The mean TTP values of mLVs-SSS and mLVs-SS in PD patients were significantly longer than those in MSA,PSP-RS patients and NC(all P<0.05),the mean wash in rate values were significantly slower than those in MSA,PSP-RS patients and NC(all P<0.05),and the mean AUC values were significantly larger than those in MSA,PSP-RS patients and NC(all P<0.05)，indicating that the drainage function of mLVs in PD patients was impaired;2.Spearman simple linear correlation analysis showed that the average TTP values(r=0.7794,P<0.0001)and AUC values(r=0.6342,P<0.0001)of mLVs-SSS in PD patients were positively correlated with H&Y grading,while the average wash in rate values were negatively correlated with H&Y grading(r=-0.6823,P<0.0001).The average TTP values(r=0.5756,P<0.0001)and AUC values(r=0.2939,P=0.01)of mLVs-SS were positively correlated with H&Y grading,while the average wash in rate values were negatively correlated with H&Y grading(r=-0.2487,P=0.0303);3.ROC curve analysis showed that the mean DCE-MRI parameters of mLVs-SSS and mLVs-SS in PD patients had higher sensitivity and specificity for the differentiation between PD and AP;4.Before and after DCE-MRI examination,there were no significant differences in systolic blood pressure,diastolic blood pressure or heart rate among the four groups,and there were no significant differences in average ICA and ECA blood flow velocity and vessel diameter among the four groups(all P>0.05);5.There was no statistically significant difference in the mean cross-sectional area of mLVs-SSS and mLVs-SS among the four groups(all P>0.05).Conclusion1.The drainage function of both mLVs-SSS and mLVs-SS in PD patients were impaired,and the drainage speed was slowed down.2.The severity of impaired mLVs drainage function in PD patients was positively correlated with H&Y grading,which indicated that severity of impaired mLVs drainage function in PD patients was correlated with the severity of illness.3.The DCE-MRI parameters of mLVs-SSS and mLVs-SS in PD patients have higher sensitivity and specificity for differentiating PD from MSA and PSP.