Management of Motor Complications in Parkinson Disease: Current and Emerging Therapies

ObjectiveTo investigate the kinetics and metabolism of caffeine in serum from patients with Parkinson disease (PD) and controls using liquid chromatography–mass spectrometry.MethodsLevels of caffeine and its 11 metabolites in serum from 108 patients with PD and 31 age-matched healthy controls were examined by liquid chromatography–mass spectrometry. Mutations in caffeine-associated genes were screened by direct sequencing.ResultsSerum levels of caffeine and 9 of its downstream metabolites were significantly decreased even in patients with early PD, unrelated to total caffeine intake or disease severity. No significant genetic variations in CYP1A2 or CYP2E1, encoding cytochrome P450 enzymes primarily involved in metabolizing caffeine in humans, were detected compared with controls. Likewise, caffeine concentrations in patients with PD with motor complications were significantly decreased compared with those without motor complications. No associations between disease severity and single nucleotide variants of the ADORA2A gene encoding adenosine 2A receptor were detected, implying a dissociation of receptor sensitivity changes and phenotype. The profile of serum caffeine and metabolite levels was identified as a potential diagnostic biomarker by receiver operating characteristic curve analysis.ConclusionAbsolute lower levels of caffeine and caffeine metabolite profiles are promising diagnostic biomarkers for early PD. This is consistent with the neuroprotective effect of caffeine previously revealed by epidemiologic and experimental studies.Classification of evidenceThis study provides Class III evidence that decreased serum levels of caffeine and its metabolites identify patients with PD.

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Pathophysiology of Motor Complications in Parkinson Disease

Archives of Neurology ◽

10.1001/archneur.64.1.137 ◽

2007 ◽

Vol 64 (1) ◽

pp. 137 ◽

Cited By ~ 12

Author(s):

Gurutz Linazasoro

Keyword(s):

Parkinson Disease ◽

Motor Complications

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Palliative Management of Parkinson Disease: Focus on Nonmotor, Distressing Symptoms

Journal of Pharmacy Practice ◽

10.1177/0897190008318370 ◽

2008 ◽

Vol 21 (4) ◽

pp. 262-272 ◽

Cited By ~ 2

Author(s):

Jack J. Chen ◽

Dominick P. Trombetta ◽

Hubert H. Fernandez

Keyword(s):

Parkinson Disease ◽

Long Term Care ◽

Functional Dependence ◽

Care Facility ◽

The United States ◽

Elderly Persons ◽

Motor Complications ◽

Term Care ◽

Increased Risk

Parkinson disease is a progressive neurodegenerative disease that commonly affects elderly persons. In the absence of neuroprotective or curative therapies, currently available therapies only provide symptomatic benefit. Progression to advanced Parkinson disease is often accompanied by functional dependence with increased risk of admission to a long-term care facility. The prevalence of Parkinson disease in long-term care facilities, within the United States, has been estimated to be between 5.2% and 10%. Patients with advanced Parkinson disease also experience other distressing motor and nonmotor conditions, such as motor complications, dementia, depression, gastrointestinal distress, orthostatic hypotension, pain, and psychosis, which can be a challenge for clinicians to manage. The presence of distressing symptoms along with the fact that Parkinson disease remains incurable necessitate discussion on a palliative care approach to this disorder. This article discusses the symptomatic management of distressing symptoms encountered in the long-term care resident with Parkinson disease, including motor complications and nonmotor features.

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Experimental Models and New, Emerging Therapies for Parkinson Disease

Principles and Practice of Movement Disorders ◽

10.1016/b978-0-443-07941-2.50012-7 ◽

2007 ◽

pp. 205-231

Author(s):

Stanley Fahn ◽

Joseph Jankovic ◽

Mark Hallett ◽

Peter Jenner

Keyword(s):

Parkinson Disease ◽

Experimental Models ◽

Emerging Therapies

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Quality of life predicts outcome of deep brain stimulation in early Parkinson disease

Neurology ◽

10.1212/wnl.0000000000007037 ◽

2019 ◽

Vol 92 (10) ◽

pp. e1109-e1120 ◽

Cited By ~ 18

Author(s):

W.M. Michael Schuepbach ◽

Lisa Tonder ◽

Alfons Schnitzler ◽

Paul Krack ◽

Joern Rau ◽

...

Keyword(s):

Quality Of Life ◽

Deep Brain Stimulation ◽

Parkinson Disease ◽

Brain Stimulation ◽

Motor Complications ◽

Baseline Characteristics ◽

Stn Dbs ◽

Disease Specific ◽

Deep Brain

ObjectiveTo investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications.MethodsWe performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson’s Disease Rating Scale (UPDRS) (UPDRS-III “off” and “on” medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI.ResultsPDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups (p < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group.ConclusionImpaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS.Clinicaltrials.gov identifierNCT00354133.

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Predictors of Mortality in Nondemented Patients With Parkinson Disease: Motor Symptoms Versus Nonmotor Symptoms

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/0891988717743589 ◽

2017 ◽

Vol 31 (1) ◽

pp. 19-26 ◽

Cited By ~ 6

Author(s):

D. Santos-García ◽

E. Suárez-Castro ◽

J. Ernandez ◽

I. Expósito-Ruiz ◽

C. Tuñas-Gesto ◽

...

Keyword(s):

Parkinson Disease ◽

Rating Scale ◽

Evaluation Study ◽

Motor Symptoms ◽

Motor Complications ◽

Nonmotor Symptoms ◽

Predictors Of Mortality ◽

Hazard Ratios ◽

Long Term Follow Up

Background and Objective: The aim of this study is to identify risk factors for mortality in a community-based cohort of nondemented patients with Parkinson disease (PD) during prospective long-term follow-up, while also comparing the effect of motor complications to nonmotor symptoms (NMS) on risk of mortality. Methods: One hundred forty seven nondemented patients with PD (57.1% males; 70.9 ± 8.6 years old) were included in this 48 month follow-up, longitudinal, single, evaluation study. Motor and therapy-related complications were assessed using the Unified Parkinson’s Disease Rating Scale/part-IV (UPDRS-IV). Non-Motor Symptoms Scale (NMSS) total score was used to assess NMS burden. Cox proportional hazard models were applied to identify independent predictors of mortality during follow-up. Results: Twenty-two patients of 146 (15.1%) died (1 case without information). Both UPDRS-IV and NMSS total scores were higher at baseline in patients with PD who died (3.5 ± 3.1 vs 2.4 ± 2.4, P = .049 and 96.9 ± 58.6 vs 61.9 ± 51.0, P = .004, respectively). Unadjusted hazard ratios (HRs) associated with UPDRS-IV and NMSS total scores among those who died during follow-up were 1.171 (95% confidence interval [CI]: 1.012-1.357; P = .035) and 1.008 (95% CI: 1.002-1.013; P = .006), respectively. Independent predictors of mortality during follow-up after adjusting for other covariates were UPDRS-IV (HR: 1.224; 95% CI: 1.002-1.494; P = .047), age (HR: 1.231; 95% CI: 1104-1.374; P < .0001), and comorbidity (Charlson Index; HR: 1.429; 95% CI: 1.023-1.994; P = .036), but not NMSS total score (HR: 1.005; 95% CI: 0.996-1.014; P = .263). Conclusions: Both motor complications (UPDRS-IV) and NMS (NMSS) were associated with mortality at 4 years, being motor complications an independent predictor of it.

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