ABSTRACT
Multiple system atrophy (MSA) and Parkinson's disease (PD) have clinical overlapping symptoms, which makes differential diagnosis difficult. Our research aimed to distinguish MSA from PD using corneal confocal microscopy (CCM), a noninvasive and objective test. The study included 63 PD patients, 30 MSA patients, and 31 healthy controls (HC). When recruiting PD and MSA, questionnaires were conducted on motor and non-motor functions, such as autonomic and cognitive functions. Participants underwent CCM to quantify the corneal nerve fibers. Corneal nerve fiber density (CNFD) and corneal nerve fiber length (CNFL) values in MSA are lower than PD (MSA vs. PD: CNFD, 20.68 ± 6.70 vs. 24.64 ± 6.43 no./mm2, p < 0.05; CNFL, 12.01 ± 3.25 vs. 14.17 ± 3.52 no./mm2, p < 0.05). In MSA + PD (combined), there is a negative correlation between CNFD and the Orthostatic Grading Scale (OGS) (r = -0.284, p = 0.007). Similarly, CNFD in the only MSA group was negatively correlated with the Unified Multiple System Atrophy Rating Scale I and II (r = -0.391, p = 0.044; r = -0.382, p = 0.049). CNFD and CNFL were inversely associated with MSA (CNFD: ß = -0.071; OR, 0.932; 95% CI, 0.872 ~ 0.996; p = 0.038; CNFL: ß = -0.135; OR, 0.874; 95% CI, 0.768-0.994; p = 0.040). Furthermore, we found the area under the receiver operating characteristic curve (ROC) of CNFL was the largest, 72.01%. The CCM could be an objective and sensitive biomarker to distinguish MSA from PD. It visually reflects a more severe degeneration in MSA compared to PD.
ABSTRACT
BACKGROUND: This study set out to investigate the relationship between serum neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and various non-motor symptoms (NMSs) in patients with Parkinson's disease (PD). METHODS: The study included 37 healthy controls (HCs) and 51 PD patients. Clinical assessments of PD symptoms were conducted for all PD patients. The NMSS was utilised to evaluate the NMS burden (NMSB) in individuals. Based on the severity of NMSB, we further categorised the PD group into two subgroups: mild-moderate NMSB group and severe-very severe NMSB group. The amounts of NFL and GFAP in the serum were measured using an extremely sensitive single molecule array (Simoa) method. Statistical analyses were performed on the collected data using SPSS 26.0 and R (version 3.6.3). RESULTS: Serum GFAP and NFL levels in the PD group with severe-very severe NMSB were significantly higher than those in the mild-moderate NMSB group (GFAP: P < 0.007; NFL: P < 0.009). Serum NFL and GFAP levels had positive correlations with NMSS total scores (GFAP: r = 0.326, P = 0.020; NFL: r = 0.318, P = 0.023) and multiple subdomains. The relationship between the attention/memory domains of NMSS and NFL levels is significantly positive (r = 0.283, P = 0.044). Similarly, the mood/apathy domains of NMSS are also significantly positively correlated with GFAP levels (r = 0.441, P = 0.001). Patients with emotional problems or cognitive impairment had higher GFAP or NFL levels, respectively. Furthermore, it has been demonstrated that NMSs play a mediating role in the quality of life of patients with PD. Moreover, the combination of NFL and GFAP has proven to be more effective than using a single component in identifying PD patients with severe-very severe NMSB. CONCLUSIONS: The severity of NMSs in PD patients, particularly cognitive and emotional symptoms, was found to be associated with the levels of serum NFL and GFAP. This study marks the first attempt to examine the connection between NMSs of PD and the simultaneous identification of NFL and GFAP levels.
