Cerebrovascular disease associated with Parkinson’s disease in Moldovan cohort study

Background: Parkinson’s disease (PD) is frequently associated with brain vascular lesions (BVLs), which may influence the severity of the disease. Material and methods: BVLs on MRI were determined in 78.4% of 111 consecutive PD patients (mean age 64.87 ± 7.69 y.o.; disease duration 50.21 ± 38.61 mo.; 48 women (43.2%), 63 men (56.8%)). Results: White matter lesions were present in 73 patients (p.) (65.77%): 61p. (54.95%) – deep white matter, 46p. (41.44%) – periventricular white matter, and 41p. (36.94%) – both locations. Lacunas were determined in 19p. (17.12%), cerebral fissures deepening – 52p. (46.85) %), perivascular spaces dilation – 34p. (30.63%), ventricular system dilation – 29p. (26.13%). Patients with and without BVLs had similar ages, ages at PD onset and disease duration. They had insignificantly higher Beck (7.26 ± 5.62 vs 6.86 ± 4.34), PDQ39 (Parkinson’s Disease Questionnaire) (59.71 ± 20.38 vs 51.94 ± 27.69) and NMS (Non-Motor Symptoms) (75.06 ± 45.21 vs 71.67 ± 26.35) scores; and lower MoCA (Montreal Cognitive Assessment) scores (21.92 ± 4.25 vs 22.38 ± 4.57). QRISK3 scores (19.68 ± 16.16 vs 12.90 ± 6.58) and levodopa equivalent daily dose (639.98 ± 223.05 vs. 439.69 ± 404.87) were significantly higher in patients with BVLs. Conclusions: Brain vascular lesions were common in our PD patients, and were associated with higher QRISK3 scores and higher levodopa equivalent daily dose, suggesting more disease severity

Axial Impairment Following Deep Brain Stimulation in Parkinson’s Disease: A Surgicogenomic Approach

Background: Postoperative outcome following deep brain stimulation (DBS) of the subthalamic nucleus is variable, particularly with respect to axial motor improvement. We hypothesized a genetic underpinning to the response to surgical intervention, termed “surgicogenomics”. Objective: We aimed to identify genetic variants associated with clinical heterogeneity in DBS outcome of Parkinson’s disease (PD) patients that could then be applied clinically to target selection leading to improved surgical outcome. Methods: Retrospective clinical data was extracted from 150 patient’s charts. Each individual was genotyped using the genome-wide NeuroX array tailored to study neurologic diseases. Genetic data were clustered based on surgical outcome assessed by comparing pre- and post-operative scores of levodopa equivalent daily dose and axial impairment at one and five years post-surgery. Allele frequencies were compared between patients with excellent vs. moderate/poor outcomes grouped using a priori defined cut-offs. We analyzed common variants, burden of rare coding variants, and PD polygenic risk score. Results: NeuroX identified 2,917 polymorphic markers at 113 genes mapped to known PD loci. The gene-burden analyses of 202 rare nonsynonymous variants suggested a nominal association of axial impairment with 14 genes (most consistent with CRHR1, IP6K2, and PRSS3). The strongest association with surgical outcome was detected between a reduction in levodopa equivalent daily dose and common variations tagging two linkage disequilibrium blocks with SH3GL2. Conclusion: Once validated in independent populations, our findings may be implemented to improve patient selection for DBS in PD.

Stability of MDS-UPDRS Motor Subtypes Over Three Years in Early Parkinson's Disease

Background: Various classifications have been proposed to subtype Parkinson's disease (PD) based on their motor phenotypes. However, the stability of these subtypes has not been properly evaluated.Objective: The goal of this study was to understand the distribution of PD motor subtypes, their stability over time, and baseline factors that predicted subtype stability.Methods: Participants (n = 170) from two prospective cohorts were included: the Early PD Longitudinal Singapore (PALS) study and the National Neuroscience Institute Movement Disorders Database. Early PD patients were classified into tremor-dominant (TD), postural instability and gait difficulty (PIGD), and indeterminate subtypes according to the Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) criteria and clinically evaluated for three consecutive years.Results: At baseline, 60.6% patients were TD, 12.4% patients were indeterminate, and 27.1% patients were PIGD subtypes (p < 0.05). After 3 years, only 62% of patients in TD and 50% of patients in PIGD subtypes remained stable. The mean levodopa equivalent daily dose (LEDD) was higher in the PIGD subtype (276.92 ± 232.91 mg; p = 0.01). Lower LEDD [p < 0.05, odds ratio (OR) 0.99, 95% confidence interval (CI): 0.98–0.99] and higher TD/PIGD ratios (p < 0.05, OR 1.77, 95% CI: 1.29–2.43) were independent predictors of stability of TD subtype with an area under the curve (AUC) of 0.787 (95%CI: 0.669–0.876), sensitivity = 57.8%, and specificity = 89.7%.Conclusion: Only 50–62% of PD motor subtypes as defined by MDS-UPDRS remained stable over 3 years. TD/PIGD ratio and baseline LEDD were independent predictors for TD subtype stability over 3 years.

Malnutrition and related factors in Filipino patients with Parkinson’s disease: results from a pilot study

Aim: Emerging evidence demonstrates a bidirectional relationship between nutritional status and Parkinson’s disease (PD). Our aim was to determine the local prevalence of malnutrition and associated factors among Filipino PD patients. Materials & methods: We assessed the nutritional status of 95 PD patients using the body mass index (BMI) and Subjective Global Assessment (SGA) and identified malnutrition-associated factors. Results & conclusion: In our sample, the mean BMI was 24.5 ± 4.2 kg/m2. Consistent with published estimates, five (5.3%) patients were classified as underweight and 57 (60%) patients were classified as overweight/obese. A total of 30 (31.6%) patients had abnormal nutritional status based on SGA. Weight-adjusted levodopa equivalent daily dose was a significant factor (p = 0.032) for BMI, while dysphagia and higher weight-adjusted levodopa equivalent daily dose were found to be predictive of abnormal nutritional status using SGA (adjusted odds ratio of 8.85 [95% CI: 1.59–49.17; p = 0.015] and 1.10 [95% CI: 1.02–1.20; p = 0.021], respectively).

Cohort Study in Parkinsonism: Delayed Transit, Accelerated Gastric Emptying, and Prodromal Dysmotility

ABSTRACTObjectives:To evaluate gastric emptying and colonic transit in a cohort of patients with Parkinson disease and other parkinsonism disorders, and to determine whether abnormal gut transit precedes motor-onset of parkinsonism.Methods:Medical record review of 84 patients with parkinsonism who underwent clinically-indicated transit studies at Mayo Clinic (2001-2019); and 11 patients with transit studies who subsequently developed parkinsonism. Data are summarized as median (IQR).Results:The 84 patients (52% female) with parkinsonism were aged 72 (66, 76) years with a disease duration of 5 (2, 8) years: Parkinson disease=70, multiple system atrophy=7, dementia with Lewy bodies=4, progressive supranuclear palsy=2, parkinsonian syndrome=1. Ten had delayed GE, 10 slow colonic transit, 16 accelerated GE (14 Parkinson disease, 1 multiple system atrophy, 1 parkinsonian syndrome), and 49 normal transit. One parkinsonian syndrome patient had both slow colonic and accelerated gastric transit. Longer disease duration and higher levodopa equivalent daily dose were observed for Parkinson disease compared to other parkinsonisms and with slow compared to normal colonic transit. Of 11 patients (5 female) with transit studies who later developed motor parkinsonism after 4 (3, 5) years: 1 had accelerated GE, 1 had delayed GE, and 1 had both delayed GE and colonic transit.Conclusions:Accelerated GE was newly identified in patients with parkinsonism, in addition to delayed GE or colonic transit. Furthermore, gut dysmotility was objectively identified to precede the motor-onset of parkinsonism.

Association of Serum Indirect Bilirubin Concentrations with Motor Subtypes of Parkinson’s Disease

Introduction: We aimed to investigate the change of serum indirect bilirubin (IBIL) concentrations in patients with Parkinson’s disease (PD) and whether IBIL concentrations were associated with the motor subtypes of PD. Methods: A case-control study was performed to evaluate differences in bilirubin concentrations between 78 PD subjects and 78 controls. Venous blood samples were collected, and total bilirubin (TBIL), direct bilirubin (DBIL), and IBIL concentrations were analyzed between PD subjects and controls. PD patients were classified into three motor subtypes: tremor-dominant (TD), intermediate (I), and postural instability and gait disorder (PIGD). It was evaluated whether there were differences in IBIL concentrations between the different motor subtypes and between motor subtypes and controls. Results: PD patients had lower IBIL concentrations compared to controls (6.51 ± 4.03 vs. 10.82 ± 4.61, p< 0.001). There was no significant difference in IBIL concentrations between PD males and PD females (6.66 ± 3.64 vs. 6.22 ± 4.79, p =0.655). IBIL concentrations had negative relationships with levodopa-equivalent daily dose (LEDD) (R = –0.452, p < 0.001) and positive relationships with tremor score (R = 0.360, p = 0.001). IBIL concentrations were significantly lower for PIGD than for TD subtype (4.88 ± 4.03 vs. 9.00 ± 4.15, p< 0.001). The lower IBIL concentrations in PD compared to controls were mainly driven by the PIGD patients. Conclusions: PD subjects showed lower levels of IBIL compared to controls. Higher IBIL levels were associated with TD motor subtype in PD, which could be related to the antioxidative properties of IBIL.