The Study Of Corneal Nerve Fiber In Patients With Parkinson's Disease

Background and Aims:The cardinal manifestations of motor symptoms of PD are bradykinesia,rest tremor,muscle stiffness,and posture instability and gait disorder,while cognitive impairment,psychiatric presentation,gastrointestinal symptom,autonomic dysfunction,hyposmia,sleep problems are the mainstay of non-motor symptoms.The traditional view is that PD is the central nervous system disease,but research has found that PD can also affect the peripheral nervous system.the overall incidence is 19% to 35%.Peripheral neuropathy increases the chance of fall,affect balance and gait,thus seriously affects the quality of life in affected PD patients.Neural conduction studies are considered to be a reliable method for the diagnosis of peripheral neuropathy,but it can only evaluate large myelinated nerve fibers.However,the ability to assess the damage of small nerve fibers,especially after therapeutic intervention,is limited.Quantitative sensory testing(QST)is non-invasive,easy to be carried out and has a good repeatability,but its shortcoming is that the subjective coordination of patients has a greater impact on the final results.The intraepidermal nerve fiber density(IENFD)is considered as the most objective index for the diagnosis and quantification of small fiber neuropathy,but the invasive character limited its clinical application.Therefore,there is an urgent need for a non-invasive,stable and sensitive detection method for the diagnosis of small fiber neuropathy in Parkinson's disease.Corneal confocal microscopy(CCM)is a new type of real-time,non-invasive,high precision and high magnification in vivo technology,which can be used to detect and evaluate the progress of systemic diseases with peripheral neuropathy in the early stage of disease,such as diabetic peripheral neuropathy,diabetic retinopathy and other small fiber neuropathy.Corneal confocal microscopy(CCM)is a new type of real-time,non-invasive,high precision and high magnification in vivo technology,which can be used to detect and evaluate the progress of systemic diseases with peripheral neuropathy in the early stage of disease,such as diabetic peripheral neuropathy,diabetic retinopathy a nd other small fiber neuropathy.The objectives of this study were to:(1)determine whether there is significant corneal nerve fiber change in patients with PD compared to age-matched controls with non-invasive,intuitive CCM.(2)define the utility of CCM in diagnosing PD,Parkinson's plus syndrome and Secondary parkinsonism.(3)determine the association between corneal nerve fiber measurements with clinical characters.Materials and Methods:43 patients with Parkinson's disease,17 patients with parkinsonism(10 Va P,8 DIP),14 patients with Parkinson's plus syndrome(7 MSA,7 PSP)and 21 healthy patients who were recruited from the Henan Provincial People's Hospital between March 2018 and October 2019.Collect clinical characteristics of all subjects: age,gender,education level,disease duration,levodopa equivalent dose.All patients evaluated UPDRS,Hoehn-Yahr staging,Mini Mental State Examination,Montreal Cognitive Assessment,14-item Hamilton anxiety rating scale,the 24-item Hamilton Depression rating scale,the scale for outcomes Parkinson's disease for autonomic symptoms and olfactory in the “open phase”.Detection of a-syn and p-syn concentrations in plasma.Corneal confocal microscope was used to detect the corneal nerve fibers in the eyes of the subjects,and pictures of the basal nerve were collected in the central area of the cornea.The best quality 4-6 pictures were selected,and the semi-automatic corneal nerve analysis software CCMetrics was used for image analysis.Corneal nerve fiber parameters include: corneal nerve fiber density;corneal nerve branch density;corneal nerve fiber length;corneal nerve fiber tortuosity.Parameters were analyzed with analysis of variance using Bonferroni as post hoc test in the case of gaussian distribution of data,Kruskal-Wallis with Dunn as post hoc test of nongaussian distribution for comparison of multiple groups.Bivariate correlation analysis using Pearson or Spearman rank correlation analysis.Results:PD group had a significantly lower CNFD compared to the HC group,PDS group and PPS group.There were no significant differences in CNFD between HC group,PDS group and PPS group.PD group had a significantly higher CNBD and CNFT compared to the HC group and PDS group.CNFD was associated with UPDRS-?,MoCA,MMSE and olfactory;CNFD was negatively associated with p-syn;CNBD was associated with MoCA and MMSE;CNFL was associated with UPDRS-?,MoCA and MMSE.The area under the ROC curve to distinguish PD from HC with CNFD,CNBD and CNFT was 95.13%,70.93% and 77.35% respectively,and for PD from PDS it was 84.13%,71.89%and 73.12% respectively,and for PD from PPS it was 81.56%,63.54% and 62.13% respectively.The area under the ROC curve to distinguish PD from HC with Olfactory detection was 82.50%.The area under the ROC curve to distinguish PD from HC with Olfactory detection combining with CNFD was 96.23%.Conclusions:1.CNFD decreased but CNBD increased,and CNFD was not associated with levodopa drugs in patients with PD,these showed that small nerve fibers are damaged in PD patients,which was an intrinsic feature of PD,and neurodegeneration and regeneration coexisted.2.PD patients had a significantly lower CNFD compared to the HC,PDS patients and PPS patients,The ROC curve analysis suggests that CNFD may have a good discriminative power to distinguish between PD patients and HC,PDS patients,PPS patients,which suggests that CNFD may be a marker for PD diagnosis and differential diagnosis.3.CNFD related with UPDRS-III?MoCA,which suggested small fiber neuropathy increased with motor symptoms and cognitive dysfunction increasing.4.CNFD combined with olfactory detection can be used for early diagnosis of PD.