Motor subtypes and clinical characteristics in sporadic and genetic Parkinson's disease groups: analysis of the PPMI cohort.

Introduction: The extensive clinical variations observed in Parkinson's disease (PD) pose challenges in early diagnosis and treatment initiation. However, genetic research in PD has significantly transformed the clinical approach to its treatment. Moreover, researchers have adopted a subtyping strategy based on homogeneous clinical symptoms to improve clinical diagnosis and treatment approaches. We conducted a study to explore clinical characteristics in genetic PD groups with motor symptom subtyping. Methods: Data was driven from the Parkinson's Progression Markers Initiative (PPMI) database. The sporadic PD (sPD) group and the genetic PD group including patients with leucine-rich kinase 2 (LRRK2) or glucosylceramidase ß (GBA) mutations were analyzed. Motor subtyping was performed using Movement Disorder Society-Unified Parkinson's disease rating scale (MDS-UPDRS) scores. I-123 FP-CIT SPECT scans were used to calculate specific binding ratios (SBRs) in the caudate and putamen. Clinical symptoms of each group were also compared. Results: MDS-UPDRS III scores were lower in the LRRK2 group, compared with the GBA and sPD group (P < 0.001), but no significant differences in striatal SBRs. The putaminal SBR value of the LRRK2 group was higher than the sPD group (P < 0.05). Within the GBA group, we observed lower SBR values in the postural instability/gait difficulty (PIGD) subtype GBA group compared to the tremor-dominant (TD) subtype GBA group (P < 0.05). The TD subtype GBA group exhibited superior putaminal SBRs compared to the TD subtype sPD group (P < 0.05). The TD subtype LRRK2 group had better putaminal SBR values (P < 0.001) and MDS-UPDRS Part III scores (P < 0.05) compared to the TD sPD group. Discussions: Our subtyping approach offers valuable insights into the clinical characteristics and progression of different genetic PD subtypes. To further validate and expand these findings, future research with larger groups and long-term follow-up data is needed. The subtyping strategy based on motor symptoms holds promise in enhancing the diagnosis and treatment of genetic PD.

Spontaneous AICA Dissection Presenting With Isolated Audiovestibular Loss.

This case report describes a man in his 40s with spontaneous anterior inferior cerebellar artery (AICA) dissection after presenting with right-sided sensorineural hearing loss.

Serial changes of I-123 FP-CIT SPECT binding asymmetry in Parkinson's disease: Analysis of the PPMI data.

Background: Dopaminergic denervation and motor symptoms are usually asymmetric at the onset of Parkinson's disease (PD). In this study, we estimated the asymmetry of specific binding ratio (SBR) of I-123 FP-CIT SPECT images during 4-years of follow up, to demonstrate the pattern of serial changes of asymmetry. Methods: Clinical and I-123 FP-CIT SPECT image data of 301 PD patients and 141 normal controls were reviewed from the Parkinson's Progression Markers Initiative cohort. I-123 FP-CIT SPECT images were taken at baseline, 1-, 2-, and 4-year follow up periods for PD patients, and at baseline for normal controls. Asymmetry index were calculated by two methods. Method 1, by using the ratio of absolute difference of right and left SBRs to the average SBR. Method 2, by using the ratio of absolute difference of right and left SBRs to the SBR values of age-matched normal controls. Results: Asymmetry index by method 2 revealed a more significant decrease during the 4-year follow up period, compared with method 1. The baseline asymmetry index of the putamen by method 2 showed significant correlation with the non-dominant putamen SBRs. However, there were no significant correlation with the baseline asymmetry index by method 2 and motor symptoms, cognition, nor autonomic symptoms. Conclusion: We suggest a novel asymmetry index in association to age-matched normal SBR values. This novel index could be adopted in predicting and evaluating the natural course of PD.

Correlation of Dopaminergic Denervation and the Progression of Autonomic Dysfunctions in Different Clinical Subtypes of Parkinson's Disease.

BACKGROUND: Autonomic dysfunctions occur in the early stage of Parkinson's disease (PD) and impact the quality of life during the progression of the disease. In this study, we evaluated the serial progression of autonomic dysfunctions between different subtypes of a prospective PD cohort. MATERIALS AND METHODS: From the Parkinson's Progression Markers Initiative (PPMI) database, 325 PD patients (age: 61.2 ± 9.7, M : F = 215 : 110) were enrolled. Patients were subgrouped into tremor-dominant (TD), indeterminate, and postural instability and gait disorder (PIGD) subtypes. The progression of autonomic dysfunctions and dopaminergic denervation from I-123 FP-CIT SPECT images of each group were analyzed and compared at baseline, 12 months, 24 months, and 48 months of follow-up periods. RESULTS: The SCOPA-AUT score of the indeterminate subtype was significantly higher than that of the TD subtype (P < 0.05) at baseline and was significantly higher than that of both TD and PIGD subtypes (P < 0.05) at 48 months. The indeterminate subtype had the most significant correlation between the aggravation of dopaminergic denervation in I-123 FP-CIT SPECT images and the increase of SCOPA-AUT scores during 48 months of follow-up (r = 0.56, P < 0.01). CONCLUSIONS: Autonomic dysfunctions were most severe in the indeterminate subtype throughout the 48 months of the follow-up period, with a significant correlation with dopaminergic denervation. We suggest a positive relationship between dopaminergic denervation and autonomic dysfunctions of the indeterminate subtype, beginning from the early stage of PD.