Parkinson's Disease and development of levodopa induced motor complications: Influence of baseline features and first medical approach

Rafael, Alexandra Sofia Rua; Barbosa, Joselina; Rosas, Maria José; Garrett, Maria Carolina

doi:10.1016/j.pbj.2016.08.001

Cited by 7 publications

(7 citation statements)

References 41 publications

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“…Parkinson’s disease (PD) is the most common and complex age-related chronic neurodegenerative movement disorder [ 1 , 2 , 3 , 4 ], hallmarked by the progressive loss of about 50–70% of dopamine neurons in the substantia nigra pars compacta (SNpc) and the reduction of dopamine (DA) in the caudate-putamen (CPu, striatum) [ 5 , 6 , 7 ], associated with classical primary (akinesia, bradykinesia, tremor, rigidity, and postural instability) and secondary motor symptoms (e.g., gait disturbance, micrographia, precision grip impairment, and speech problems) [ 8 , 9 , 10 , 11 ]. However, non-motor symptoms are increasingly recognized as relevant in the disease-state, given the associated alterations in mood (depression and anxiety) and cognition [ 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Antidepressant-Like Properties of Intrastriatal Botulinum Neurotoxin-A Injection in a Unilateral 6-OHDA Rat Model of Parkinson’s Disease

Antipova

Holzmann

Hawlitschka

et al. 2021

Toxins

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Parkinson’s patients often suffer from depression and anxiety, for which there are no optimal treatments. Hemiparkinsonian (hemi-PD) rats were used to test whether intrastriatal Botulinum neurotoxin-A (BoNT-A) application could also have antidepressant-like properties in addition to the known improvement of motor performance. To quantify depression- and anxiety-like behavior, the forced swim test, tail suspension test, open field test, and elevated plus maze test were applied to hemi-PD rats injected with BoNT-A or vehicle. Furthermore, we correlated the results in the forced swim test, open field test, and elevated plus maze test with the rotational behavior induced by apomorphine and amphetamine. Hemi-PD rats did not show significant anxiety-like behavior as compared with Sham 6-OHDA- + Sham BoNT-A-injected as well as with non-injected rats. However, hemi-PD rats demonstrated increased depression-like behaviors compared with Sham- or non-injected rats; this was seen by increased struggling frequency and increased immobility frequency. Hemi-PD rats intrastriatally injected with BoNT-A exhibited reduced depression-like behavior compared with the respective vehicle-receiving hemi-PD animals. The significant effects of intrastriatally applied BoNT-A seen in the forced swim test are reminiscent of those found after various antidepressant drug therapies. Our data correspond with the efficacy of BoNT-A treatment of glabellar frown lines in treating patients with major depression and suggest that also intrastriatal injected BoNT-A may have some antidepressant-like effect on hemi-PD.

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Section: Introductionmentioning

confidence: 99%

Antidepressant-Like Properties of Intrastriatal Botulinum Neurotoxin-A Injection in a Unilateral 6-OHDA Rat Model of Parkinson’s Disease

Antipova

Holzmann

Hawlitschka

et al. 2021

Toxins

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“…Parkinson's disease (PD) has a prevalence rate of 1–2 per 1,000 of the population worldwide ( 1 ). Despite L-DOPA treatment and optimal medication, around 36–50% of patients with PD will present motor complications such as dyskinesia and motor fluctuations ( 2 , 3 ), and 78% will eventually develop dementia ( 4 ), leading to various degrees of disability and reduced quality of life. In working-age adults, PD also affects their economic productivity ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of a High-Intensity Tandem Bicycle Exercise Program on Clinical Severity, Functional Magnetic Resonance Imaging, and Plasma Biomarkers in Parkinson's Disease

et al. 2020

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Rationale: The optimal modality, intensity, duration, frequency, and dose–response of exercise as a therapy for Parkinson's Disease (PD) are insufficiently understood. Objective: To assess the impact of a high-intensity tandem bicycle program on clinical severity, biomarkers, and functional MRI (fMRI) in PD. Methods: A single-center, parallel-group clinical trial was conducted. Thirteen PD patients aged 65 or younger were divided in two groups: a control group and an intervention group that incorporated a cycling program at 80% of each individual's maximum heart rate (HR) (≥80 rpm), three times a week, for 16 weeks. Both groups continued their conventional medications for PD. At baseline and at the end of follow-up, we determined in all participants the Unified Parkinson's Disease Rating Scale, anthropometry, VO 2 max, PD biomarkers, and fMRI. Results: VO 2 max improved in the intervention group (IG) (+5.7 ml/kg/min), while it slightly deteriorated in the control group (CG) (−1.6 ml/kg/min) ( p = 0.041). Mean Unified Parkinson's Disease Rating Scale (UPDRS) went down by 5.7 points in the IG and showed a small 0.9-point increase in the CG ( p = 0.11). fMRI showed activation of the right fusiform gyrus during the motor task and functional connectivity between the cingulum and areas of the frontal cortex, and between the cerebellar vermis and the thalamus and posterior temporal gyrus. Plasma brain-derived neurotrophic factor (BDNF) levels increased more than 10-fold in the IG and decreased in the CG ( p = 0.028). Larger increases in plasma BDNF correlated with greater decreases in UPDRS ( r = −0.58, p = 0.04). Conclusions: Our findings suggest that high-intensity tandem bicycle improves motor function and biochemical and functional neuroimaging variables in PD patients. Trial registration number: ISRCTN 13047118, Registered on February 8, 2018.

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“…The evidence on predictors of motor complications is variable, often contradictory, and typically from cross‐sectional studies or secondary outcomes in clinical trials of late‐stage PD . There are few longitudinal cohort studies, and even fewer are prospectively recruited …”

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confidence: 99%

“…late-stage PD. 2 There are few longitudinal cohort studies, 8,9 and even fewer are prospectively recruited. 10,11 Our aim was to identify risk factors for the onset of motor complications in the Oxford Parkinson's Disease Centre Discovery cohort, a large, prospectively recruited, clinic-based cohort of early PD participants, using a comprehensive and robust longitudinal survival analysis model.…”

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confidence: 99%

Predictors of motor complications in early Parkinson's disease: A prospective cohort study

et al. 2019

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Objective The objective of this study was to identify clinical predictors of motor complications (dyskinesia and motor fluctuations) of levodopa in a prospectively recruited PD cohort using longitudinal analysis. Methods An inception cohort (Oxford Discovery) of 734 patients was followed to a maximum of 10 years from diagnosis using a discrete‐time survival analysis. A subset analysis was used to validate an online dyskinesia‐risk calculator developed from the results of the Stalevo Reduction in Dyskinesia Evaluation PD trial. Results A total of 186 cases of dyskinesia and 254 cases of motor fluctuations were observed. Dyskinesia incidence increased with time (risk per 100 participants [95% confidence interval] 13 [11–16] <3.5 years, 16 [13–21] 3.5–5.0 years, 19 [14–26] 5–6.5 years, and 23 [16–33] >6.5 years from diagnosis). Motor complication predictors were grouped as medication predictors, disease predictors and patient predictors. Baseline nonmotor feature severity, low mood, anxiety, and age at symptom onset were associated with motor complications among a number of previously identified predictors. Replication of the Stalevo Reduction in Dyskinesia Evaluation PD calculator was reasonable with the area under the curve for dyskinesia risk score as a predictor of dyskinesia being 0.68 (95% confidence interval, 0.55–0.81). Conclusions This study quantifies risk of motor complications, finds consistent predictors, and demonstrates the novel finding that nonmotor features of PD, particularly low mood and anxiety, are significant risk factors for motor complications. Further validation of dyskinesia risk scores are required as well as evidence to determine if the routine use of such scores can be clinically valuable in enhancing patient care and quality of life. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Parkinson's Disease and development of levodopa induced motor complications: Influence of baseline features and first medical approach

Cited by 7 publications

References 41 publications

Antidepressant-Like Properties of Intrastriatal Botulinum Neurotoxin-A Injection in a Unilateral 6-OHDA Rat Model of Parkinson’s Disease

Antidepressant-Like Properties of Intrastriatal Botulinum Neurotoxin-A Injection in a Unilateral 6-OHDA Rat Model of Parkinson’s Disease

Effect of a High-Intensity Tandem Bicycle Exercise Program on Clinical Severity, Functional Magnetic Resonance Imaging, and Plasma Biomarkers in Parkinson's Disease

Predictors of motor complications in early Parkinson's disease: A prospective cohort study

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