The clinical meaning of levodopa equivalent daily dose in Parkinson's disease

Author(s):  
Charlotte Julien ◽  
Guillaume Hache ◽  
Morgane Dulac ◽  
Cléa Dubrou ◽  
Giovanni Castelnovo ◽  
...  

2021 ◽  
pp. 1-12
Author(s):  
Naomi P. Visanji ◽  
Mahdi Ghani ◽  
Eric Yu ◽  
Erfan Ghani Kakhki ◽  
Christine Sato ◽  
...  

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.



Author(s):  
Nikolai Gil D Reyes ◽  
Roland Dominic G Jamora ◽  
Marianne Rae M Baltazar ◽  
Alfand Marl F Dy Closas

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).





2019 ◽  
Vol 19 (3-4) ◽  
pp. 155-162
Author(s):  
Jun Li ◽  
Lei Zhao ◽  
Zhong Wang ◽  
Xiuying Zhao ◽  
Jian Wu

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.



2021 ◽  
Vol 64 (6) ◽  
pp. 33-36
Author(s):  
Lilia Rotaru ◽  

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



2021 ◽  
Vol 12 ◽  
Author(s):  
Abhijeet K. Kohat ◽  
Samuel Y. E. Ng ◽  
Aidan S. Y. Wong ◽  
Nicole S. Y. Chia ◽  
Xinyi Choi ◽  
...  

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 &lt; 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 &lt; 0.05, odds ratio (OR) 0.99, 95% confidence interval (CI): 0.98–0.99] and higher TD/PIGD ratios (p &lt; 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.



CNS Spectrums ◽  
2018 ◽  
Vol 23 (6) ◽  
pp. 402-413 ◽  
Author(s):  
Kevin J. Black ◽  
Henry Nasrallah ◽  
Stuart Isaacson ◽  
Mark Stacy ◽  
Rajesh Pahwa ◽  
...  

Patients with Parkinson’s disease psychosis (PDP) are often treated with an atypical antipsychotic, especially quetiapine or clozapine, but side effects, lack of sufficient efficacy, or both may motivate a switch to pimavanserin, the first medication approved for management of PDP. How best to implement a switch to pimavanserin has not been clear, as there are no controlled trials or case series in the literature to provide guidance. An abrupt switch may interrupt partially effective treatment or potentially trigger rebound effects from antipsychotic withdrawal, whereas cross-taper involves potential drug interactions. A panel of experts drew from published data, their experience treating PDP, lessons from switching antipsychotic drugs in other populations, and the pharmacology of the relevant drugs, to establish consensus recommendations. The panel concluded that patients with PDP can be safely and effectively switched from atypical antipsychotics used off label in PDP to the recently approved pimavanserin by considering each agent’s pharmacokinetics and pharmacodynamics, receptor interactions, and the clinical reason for switching (efficacy or adverse events). Final recommendations are that such a switch should aim to maintain adequate 5-HT2A antagonism during the switch, thus providing a stable transition so that efficacy is maintained. Specifically, the consensus recommendation is to add pimavanserin at the full recommended daily dose (34 mg) for 2–6 weeks in most patients before beginning to taper and discontinue quetiapine or clozapine over several days to weeks. Further details are provided for this recommendation, as well as for special clinical circumstances where switching may need to proceed more rapidly.



2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Dong Hwan Ho ◽  
Sanghak Yi ◽  
Hyemyung Seo ◽  
Ilhong Son ◽  
Wongi Seol

Parkinson’s disease (PD) is a difficult disease to diagnose although it is the second most common neurodegenerative disease. Recent studies show that exosome isolated from urine contains LRRK2 or DJ-1, proteins whose mutations cause PD. To investigate a potential use for urine exosomes as a tool for PD diagnosis, we compared levels of LRRK2,α-synuclein, and DJ-1 in urine exosomes isolated from Korean PD patients and non-PD controls. LRRK2 and DJ-1, but notα-synuclein, were detected in the urine exosome samples, as reported previously. We initially could not detect any significant difference in these protein levels between the patient and the control groups. However, when age, disease duration, L-dopa daily dose, and gender were considered as analytical parameters, LRRK2 and DJ-1 protein levels showed clear gender-dependent differences. In addition, DJ-1 level was significantly higher (1.7-fold) in male patients with PD than that in male non-PD controls and increased in an age-dependent manner in male patients with PD. Our observation might provide a clue to lead to a novel biomarker for PD diagnosis, at least in males.



2019 ◽  
Vol 8 (10) ◽  
pp. 1533
Author(s):  
Oana Maria Vanta ◽  
Nicoleta Tohanean ◽  
Sebastian Pintea ◽  
Lacramioara Perju-Dumbrava

(1) Background: Increased attention has lately been given to polyneuropathy in Parkinson’s Disease (PD). Several papers postulated that large-fiber neuropathy (PNP) in PD is related to vitamin B12 deficiency and L-Dopa exposure. (2) Methods: Using a cross-sectional, observational study, we evaluated 73 PD patients without a previously known cause of PNP using clinical scores (UPDRS II and III and Toronto Clinical Scoring System), biological evaluation of vitamin B12 and folic acid, and nerve conduction studies to assess the prevalence and features of PNP. (3) Results: The prevalence of PNP was 49.3% in the study group. In the L-Dopa group, the frequency of PNP was 67.3% as compared to PNP in the non-L-Dopa group, where one subject had PNP (χ2 = 23.41, p < 0.01). PNP was predominantly sensory with mild to moderate axonal loss. Cyanocobalamin correlated with L-Dopa daily dose (r = −0.287, p < 0.05) and L-Dopa duration of administration (r = −0.316, p < 0.05). L-Dopa daily dose correlated with the amplitudes of sensory nerve action potentials of the superficial peroneal and radial nerves (r = −0.312, p < 0.05) (r = −0.336, p < 0.05), respectively. (4) Conclusions: PNP is more frequent in L-Dopa-treated patients than in L-Dopa-naïve patients. The results imply that longer exposure to high doses of L-Dopa may cause vitamin B12 and folate imbalance and PNP, secondarily.



2021 ◽  
Vol 429 ◽  
pp. 119426
Author(s):  
Camille Carroll ◽  
Andrew Lees ◽  
Heinz Reichmann ◽  
Diogo Martins ◽  
Diogo Magalhães ◽  
...  


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