Parkinsonism & related disorders最新文献

Introduction: Efficacy of deep brain stimulation (DBS) is established for several movement and psychiatric disorders. However, the mechanism of action and local tissue changes are incompletely described. We describe neurohistopathological findings of 9 patients who underwent DBS for parkinsonism and performed a systematic literature review on postmortem pathologic reports post-DBS.

Methods: We performed a retrospective study of patients who underwent DBS for Parkinsonism between 2000 and 2023 and had postmortem neurohistopathological assessments. Demographics and clinical features were collected. Levodopa equivalent daily dose (LEDD) and total electrical energy delivered (TEED) were calculated. A systematic literature review was conducted.

Results: Postmortem assessment of 9 DBS patients was performed (7 Parkinson's disease [PD], 1 Parkinsonism, 1 Multiple System Atrophy with pre-DBS clinical diagnosis of PD). Median age at DBS was 65 years (range, 54-69), 8 were male. Subthalamic nucleus was targeted in 8 patients, globus pallidus in 1. Median DBS duration was 65 months (range, 7-264). Post-DBS LEDD reduction was found in 7/9 patients and TEED increased over time in all cases. There were no DBS-related deaths. Neurohistopathological assessment showed gliosis in 7 patients and activated microglial infiltration in 1. In the literature (between 1977 and 2021), 59 patients with postmortem post-DBS findings were identified: 26 (44 %) PD, 20 (34 %) pain, and 13 (22 %) other conditions.

Conclusion: Findings confirm presence of a local tissue reaction (gliosis and activated microglia) around the implanted leads. The effect of local changes on the clinical efficacy of DBS is not established. Further DBS postmortem studies and standardization of tissue processing are needed.

Introduction: Parkinson's disease (PD) is a progressive neurodegenerative disease, and biomarkers are needed to enhance earlier detection and monitoring. Alpha-synuclein, phosphorylated at serine 129 (pS129-α-syn), is the predominant form of α-syn found in Lewy bodies implicating an involvement in disease pathology. This review aims to systematically evaluate the evidence for pS129-α-syn detection in human biofluid samples of PD utilizing ELISA-based protein detection methods.

Methods: A systematic review was conducted following the Preferred Reported Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Electronic searches were performed in PubMed, Web of Science, and Cochrane databases from inception to November 7th, 2024, to identify studies comparing pS129-α-syn in biofluids of PD patients with controls or related neurodegenerative disease. Risk of bias was assessed for each study.

Results: Twenty-three publications met the inclusion criteria, with pS129-α-syn detected in cerebrospinal fluid, plasma, red blood cells, serum, and saliva exosomes. Overall, pS129-α-syn levels were elevated in patients with PD compared to controls, and in some studies, correlated with disease severity. There was no consistent pattern when comparing PD patients to those with related neurodegenerative diseases. Significant variability in pS129-α-syn levels and considerable overlap between groups may limit the utility as a biomarker.

Conclusion: While pS129-α-syn for PD shows some promise as a diagnostic marker for PD, its differential diagnostic utility remains limited. Further research involving larger cohorts is required. The greatest potential for pS129-α-syn may be as part of a panel with other PD-specific markers, to enhance diagnostic accuracy and prognostic value.

Olfactory dysfunction, affecting 75-90 % of Parkinson's disease (PD) patients, holds significant predictive value for PD development. Advanced imaging techniques, such as diffusion MRI (dMRI) and functional MRI (fMRI), offer insights into structural and functional changes within olfactory pathways. This review summarizes a decade of research on MRI-based connectivity of the olfactory system in PD, focusing on structural and functional alterations in olfactory brain areas and their links to early olfactory processing changes. Fifteen dMRI and eighteen fMRI studies met inclusion criteria and were carefully reviewed. Among the studies investigating diffusion metrics, the most consistent finding was the reduction of fractional anisotropy in the olfactory tract and anterior olfactory structures, though evidence correlating this result to olfactory dysfunction is limited and contrasting. dMRI support the hypothesis that olfactory function may be correlated to structural alterations at the network-level. In contrast, fMRI studies found more consistent evidence of dysconnectivity in both primary and secondary olfactory areas as directly correlated to olfactory processing and dysfunction. Results suggest a potential dissociation between structural alterations in olfactory brain regions and early functional impairment in olfactory processing, likely related to different patient subtypes. Heterogeneity in clinical and technical factors may limit the generalizability of the results, leaving room for further investigations. By providing a comprehensive perspective on the use of dMRI and fMRI to explore the olfactory connectome in PD, our review might facilitate future research towards earlier diagnosis and more targeted therapeutic and neurorehabilitation strategies.