Objective: To find means to accurately differentiate Parkinson's disease from multiple system atrophy.
Background: In early disease stages it can be clinically difficult to differentiate idiopathic Parkinson's disease (IPD) from patients with multiple system atrophy predominated by parkinsonism (MSA-P).
Methods: In CSF of 31 patients with IPD, 19 patients with MSA-P, we analyzed tau, neurofilament light chain (NFL) and heavy chain (NFHp35) and the noradrenergic metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG).
Results: CSF levels of NFL, NFHp35, and tau were significantly increased in MSA-P, whereas MHPG levels were significantly decreased in MSA-P. Optimal discriminative cut-off values for the differentiation between MSA-P and IPD were calculated resulting in high sensitivity (76-94%) and specificity (83-97%) levels. Multivariate logistic regression resulted in the combination of NFL and tau as independent contributors in differentiating between MSA-P and IPD with a 95% sensitivity and a 84% specificity.
Conclusion: Higher CSF levels of axonal markers could reflect advanced axonal degeneration in MSA-P. Differentiating MSA-P from IPD is accurately possible with CSF analysis of a combination of axonal and neurotransmitter biomarkers. Patient Characteristics Idiopathic Parkinson's Disease (nฯญ31) MSA-P (n ฯญ 19) Controls P-value Age 52.5 ฯฎ 10.8 59.6 ฯฎ 6.6 52.8 ฯฎ 9.2 0.0006 1 Age at onset 49.5 ฯฎ 10 55.7 ฯฎ 7 NA 0.02 1 Disease duration 3.6 ฯฎ 2.8 4.1 ฯฎ 2.1 NA NS 2 Modified H & Y 1.5 2.5 NA 0.0001 2 SD: Standard deviation, NA: Not applicable, NS: not significant, 1) Unpaired Student's t-test for MSA-P vs. IPD, 2) Mann Whitney test MSA-P vs. IPD values are mean ฯฎ SD unless indicated otherwise. Accuracy numbers with corresponding cutoff values CSF parameter Cutoff value MSA-Pvs IPD TAU ฯพ 227 sensitivity 76 specificity 97 ROC AUC 0.88 likelihood ratio 4.11 NFL ฯพ 17.15 sensitivity 83 specificity 90 ROC AUC 0.92 Likelihood ratio 5.42 NFHp35 ฯพ 114.5 sensitivity 83 specificity 87 ROC AUC 0.88 MHPG ฯฝ 40.5 likelihood ratio 5.23 sensitivity 94 Accuracy numbers with corresponding cutoff values CSF parameter Cutoff value MSA-Pvs IPD specificity 83 ROC AUC 0.91 Likelihood ratio 14.9 ROC AUC: receiver operating curve area under curve P2 Heterozygous PINK1 mutations are a significant risk factor in sporadic PD