[Show abstract][Hide abstract] ABSTRACT: In Parkinson’s disease (PD) subtle balance abnormalities can already be detected in early stage patients. One feature of impaired balance control in PD is asymmetry: one leg produces more corrective joint torque than the other. We hypothesize that in mild to moderately affected PD patients, the least impaired leg compensates for the more impaired leg.
20 PD patients and eleven healthy matched controls participated. Clinical asymmetry was determined by the difference between the left and right body side scores on the Unified Parkinson’s Disease Rating Scale. Balance was perturbed using two independent continuous multisine perturbations in the forward-backward direction. Subsequently, we applied closed-loop system identification, that determined the spectral estimate of the stabilizing mechanisms, for each leg.
Balance control behaviour was similar in PD patients and controls at the ankle, but at the hip stiffness was increased. Controls exhibited symmetrical balance control, but in PD patients the balance contribution of the leg of the clinically least affected body side was higher, whereas the leg of the clinically most affected body side contributed less. The ratio between both legs helped to preserve a normal motor output at the ankle.
Our results suggest that PD patients compensate for balance control asymmetries by increasing the relative contribution of the leg of their least affected body side. This compensation appears to be successful at the ankle, but is accompanied by an increased stiffness at the hip. We discuss the possible implications of these findings for postural stability and fall risk in PD patients.
Journal of Neurophysiology 09/2014; · 3.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Balance control (the ability to maintain an upright posture) is asymmetrically controlled in a proportion of patients with Parkinson's disease. Gait asymmetries have been linked to the pathophysiology of freezing of gait. We speculate that asymmetries in balance could contribute to freezing by a) hampering the unloading of the stepping leg and/or b) leading to a preferred stance leg during gait, which then results in asymmetric gait. To investigate this, we examined the relationship between balance control and weight-bearing asymmetries and freezing. We included 20 human patients with Parkinson (tested OFF medication; nine freezers) and nine healthy controls. Balance was perturbed in the sagittal plane, using continuous multi-sine perturbations, applied by a motion platform and by a force at the sacrum. Applying closed-loop system identification techniques, relating the body sway angle to the joint torques of each leg separately, determined the relative contribution of each ankle and hip joint to the total amount of joint torque. We also calculated weight-bearing asymmetries. We determined the 99-percent confidence interval of weight-bearing and balance-control asymmetry using the responses of the healthy controls. Freezers did not have larger asymmetries in weight bearing (p = 0.85) nor more asymmetrical balance control compared to non-freezers (p = 0.25). The healthy linear one-to-one relationship between weight bearing and balance control was significantly different for freezers and non-freezers (p = 0.01). Specifically, non-freezers had a significant relationship between weight bearing and balance control (p = 0.02), whereas this relation was not significant for freezers (p = 0.15). Balance control is asymmetrical in most patients (about 75 percent) with Parkinson's disease, but this asymmetry is not related to freezing. The relationship between weight bearing and balance control seems to be less pronounced in freezers, compared to healthy controls and non-freezers. However, this relationship should be investigated further in larger groups of patients. Citation: Boonstra TA, van Vugt JPP, van der Kooij H, Bloem BR (2014) Balance Asymmetry in Parkinson's Disease and Its Contribution to Freezing of Gait. PLoS ONE 9(7): e102493. doi:10.1371/journal.pone.0102493 Copyright: ß 2014 Boonstra et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the BrainGain Smart Mix Programme of the Netherlands Ministry of Economic Affairs and the Netherlands Ministry of Education, Culture and Science (www.nici.ru.nl/braingain); the Dutch Parkinson Patient Foundation (http://www.parkinson-vereniging.nl/; to T.A.B.) and the Netherlands Organization for Scientific Research (NWO) (#016076352 to B.R.B.; www.nwo.nl). The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.
[Show abstract][Hide abstract] ABSTRACT: Objective
Patients with Parkinson’s disease often experience difficulties in adapting movements and learning alternative movements to compensate for symptoms. Since observation of movement has been demonstrated to lead to the formation of a lasting specific motor memory that resembled that elicited by physical training we hypothesize that mu-rhythm desynchronization in response to movement observation is impaired in Parkinson’s disease.
In a pilot study with nine patients with Parkinson’s disease at a Hoehn and Yahr stage of I or II and eleven age-matched controls, we tested this hypothesis by comparing the event related desynchronization (ERD) patterns from the EEG recorded during the observation of hand action and baseline videos.
Healthy subjects showed normal bilateral ERD of the mu-rhythm. In patients with Parkinson’s disease this distinct ERD pattern was lacking.
The results of this study suggest that event-related mu-rhythm desynchronization is impaired in Parkinson’s disease, even at early stages of the disease.
Studying event-related mu-rhythm desynchronization dysfunction in Parkinson’s disease patients may enhance our understanding of symptoms as impaired motor learning.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 01/2014; · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ambulatory monitoring of motor symptoms in Parkinsons disease (PD) can improve our therapeutic strategies, especially in patients with motor fluctuations. Previously published monitors usually assess only one or a few basic aspects of the cardinal motor symptoms in a laboratory setting. We developed a novel ambulatory monitoring system that provides a complete motor assessment by simultaneously analyzing current motor activity of the patient (e.g. sitting, walking) and the severity of many aspects related to tremor, bradykinesia, and hypokinesia. The monitor consists of a set of four inertial sensors. Validity of our monitor was established in seven healthy controls and six PD patients treated with deep brain stimulation (DBS) of the subthalamic nucleus. Patients were tested at three different levels of DBS treatment. Subjects were monitored while performing different tasks, including motor tests of the Unified Parkinsons Disease Rating Scale (UPDRS). Output of the monitor was compared to simultaneously recorded videos. The monitor proved very accurate in discriminating between several motor activities. Monitor output correlated well with blinded UPDRS ratings during different DBS levels. The combined analysis of motor activity and symptom severity by our PD monitor brings true ambulatory monitoring of a wide variety of motor symptoms one step closer..
IEEE transactions on bio-medical engineering 05/2010; · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sialorrhea affects approximately 75% of patients with Parkinson disease (PD). Sialorrhea is often treated with anticholinergics, but central side effects limit their usefulness. Glycopyrrolate (glycopyrronium bromide) is an anticholinergic drug with a quaternary ammonium structure not able to cross the blood-brain barrier in considerable amounts. Therefore, glycopyrrolate exhibits minimal central side effects, which may be an advantage in patients with PD, of whom a significant portion already experience cognitive deficits.
To determine the efficacy and safety of glycopyrrolate in the treatment of sialorrhea in patients with PD.
We conducted a 4-week, randomized, double-blind, placebo-controlled, crossover trial with oral glycopyrrolate 1 mg 3 times daily in 23 patients with PD. The severity of the sialorrhea was scored on a daily basis by the patients or a caregiver with a sialorrhea scoring scale ranging from 1 (no sialorrhea) to 9 (profuse sialorrhea).
The mean (SD) sialorrhea score improved from 4.6 (1.7) with placebo to 3.8 (1.6) with glycopyrrolate (p = 0.011). Nine patients (39.1%) with glycopyrrolate had a clinically relevant improvement of at least 30% vs 1 patient (4.3%) with placebo (p = 0.021). There were no significant differences in adverse events between glycopyrrolate and placebo treatment.
Oral glycopyrrolate 1 mg 3 times daily is an effective and safe therapy for sialorrhea in Parkinson disease. Classification of evidence: This study provides Class I evidence that glycopyrrolate 1 mg 3 times daily is more effective than placebo in reducing sialorrhea in patients with Parkinson disease during a 4-week study.
[Show abstract][Hide abstract] ABSTRACT: To identify determinants for the discontinuation of non-ergoline dopamine agonist (DA) treatment in patients with Parkinson’s disease (PD) and to identify genetic determinants in genes encoding dopamine receptor (DR)D2 and DRD3 in a exploratory analysis.
Patients included were first-time users of the non-ergoline DA ropinirole or pramipexole who had been diagnosed with PD before 2005. Treatment discontinuation was defined as a gap of 180 days or more between two refills of the DA. Non-genetic determinants for discontinuation were studied in the overall population, and genetic determinants [DRD2 141C Ins/Del, DRD2 (CA)n STR, DRD2 TaqIA, DRD3 MscI single nucleotide polymorphism (SNP) and DRD3 MspI SNP] were studied in a subgroup. Cox proportional hazard analysis was used to estimate the hazard ratios (HR) for the discontinuation of non-ergoline DA treatment.
The study population comprised 90 patients. Apomorphine use was associated with non-ergoline DA discontinuation, although the apomorphine group consisted only of three patients [HR 6.26; 95% confidence interval (CI) 1.85–21.2]. Daily levodopa dosages between 500 and 1000 mg were positively associated with discontinuation (HR 2.31; 95% CI 1.08–4.93). Included in the exploratory pharmacogenetic analysis were 38 patients. The absence of a 15× DRD2 CA repeat allele was significantly related with a decreased discontinuation of non-ergoline treatment (HR 0.23; 95% CI 0.07–0.81). The DRD3 MspI polymorphism showed a non-significant allele dose effect, suggestive of a causal relationship.
This study identified apomorphine use and levodopa dosages between 500 and 1000 mg as non-genetic and the 15× DRD2 CA repeat allele as genetic determinants for the discontinuation of non-ergoline DA treatment in patients with PD. More research is needed to replicate these findings.
European Journal of Clinical Pharmacology 09/2009; 65(12):1245-51. · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tremor and bradykinesia are two prominent features of Parkinson’s disease (PD). Currently, these motor symptoms are evaluated
by physicians, generally using the Unified Parkinson’s Disease Rating Scale (UPDRS). In addition to these short subjective
physician’s tests, it is desirable to develop an objective, ambulant system thoroughly assessing tremor and bradykinesia accurately
This paper presents the PD monitor, a measurement system using accelerometry to quantify tremor and bradykinesia. For the
evaluation of tremor, rest tremor in the arm, thigh, and trunk and kinetic tremor in the arm were quantified. Bradykinesia
was assessed by parameters related to arm movement, walking, and standing up. An Activity Classifier was integrated, enabling
a more detailed analysis than currently available systems.
The PD monitor was validated using measurements of six PD subjects receiving deep brain stimulation in the subthalamic nucleus.
During the experiments, each patient wore four sensors while subsequently receiving three different stimulation settings:
stimulator on, stimulator on at 80% of the normal stimulation amplitude, and stimulator off. Concurrently, patients were recorded
on video, which were rated by a physician using the UPDRS.
A correlation analysis of the physician’s scores and the PD monitor demonstrated that the system accurately measured the severity
of tremor and bradykinesia whilst assessing a broad spectrum of aspects related to both symptoms.
In conclusion, the PD monitor can be used for a detailed evaluation of the PD motor symptoms in order to optimize treatment.
[Show abstract][Hide abstract] ABSTRACT: To compare characteristics and incidence of discontinuation of Parkinson's disease (PD) patients starting ropinirole or pramipexole in clinical practice with data from randomised controlled clinical trials (RCTs).
Included in the retrospective clinical-practice cohort were first-time users of ropinirole or pramipexole diagnosed with PD before 2005. Baseline characteristics and incidence of discontinuation were compared between the clinical-practice cohort and RCTs. Treatment discontinuation was defined as more than 180 days between two refills of ropinirole or pramipexole. The incidence of discontinuation in RCTs was based on the reported rate of discontinuation for any cause.
Included were 45 patients who started with ropinirole and 59 patients who started with pramipexole. Treatment was discontinued within 3 years in 51% (ropinirole) and 60% (pramipexole) of the patients. Ten RCTs with ropinirole and 12 with pramipexole were identified. Baseline characteristics did not differ between the clinical-practice cohort and RCTs. RCTs reported discontinuation rates comparable with those at the same timepoint in the clinical practice until 1 year of follow-up.
This study shows that the overall incidence of discontinuation of ropinirole and pramipexole between the patients in our clinical-practice cohort and patients in the RCTs was comparable for the short term. However for the long term, discontinuation in practice is possibly higher.
European Journal of Clinical Pharmacology 08/2008; 64(10):1021-6. · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Discontinuation of ropinirole or pramipexole by Parkinson patients. Patient characteristics and incidence in daily clinical practice compared with clinical trials Objective To compare characteristics and incidence of therapy discontinuation by Parkinson (PD) patients starting ropinirole or pramipexole in clinical practice with data from randomised controlled clinical trials (RCTs). Secondly, to identify determinants of discontinuation of ropinirole and pramipexole in daily clinical practice. Design and methods Included in the clinical practice cohort were first time users of ropinirole or pramipexole diagnosed with PD before 2005. Baseline characteristics and incidence of discontinuation were compared between the clinical practice cohort and RCTs. Treatment discontinuation was defined as more than 180 days between two refills of ropinirole or pramipexole. The incidence of discontinuation in RCTs was based on the reported rate of discontinuation of whatever cause. Determinants for discontinuation of ropinirole and pramipexole were identified. Results Included were 45 patients who started ropinirole and 59 patients who started pramipexole. Treatment was discontinued within 3 years in 51 % (ropinirole) and 60 % (pramipexole) of the patients. Ten RCTs with ropinirole and twelve with pramipexole were identified. Baseline characteristics did not differ between the clinical practice cohort and RCTs. RCTs reported discontinuation rates comparable with those at the same time point in the clinical practice cohort until 5 years of follow-up for ropinirole and until 1 year of follow-up for pramipexole. We could not identify determinants for discontinuation. Conclusion This study shows that the overall incidence of discontinuation of ropinirole and pramipexole between the patients in our clinical practice cohort and patients in the RCTs were comparable. Genetic determinants for discontinuation have not been studied until now.
[Show abstract][Hide abstract] ABSTRACT: Pharmacotherapy is the mainstay in the treatment of Parkinson's disease and the armamentarium of drugs available for the therapy of this disease is still expanding. Anti-Parkinson's disease drugs are effective in reducing the physical symptoms, such as hypokinesia, bradykinesia, rigidity and tremor. However, there is a large interindividual variability in response to anti-Parkinson's disease drugs with respect to both drug efficacy and toxicity. It is thought that genetic variability in genes encoding drug-metabolizing enzymes, drug receptors and proteins involved in pathway signaling is an important factor in determining interindividual variability in drug response. Pharmacogenetics aims at identifying genetic markers associated with drug response. Ideally, knowledge of these genetic markers will enable us to predict an individual's drug response in terms of both efficacy and toxicity. The role of pharmacogenetics in the treatment of Parkinson's disease is relatively unexplored. Therefore, we aim to present a systematic review of the published pharmacogenetic studies in Parkinson's disease and to describe polymorphic genes of interest for future research.
[Show abstract][Hide abstract] ABSTRACT: Cognitive processes can influence balance in various ways, but not all changes in postural performance can easily be identified with the naked clinical eye. Various studies have shown that dynamic posturography is able to detect more subtle changes in balance control. For patients with Parkinson's disease (which is typically an asymmetric disease), changes in the symmetry of balance control might provide a sensitive measure of cognitive influences on balance. Here, we describe a new posturography technique that combines dynamic platform perturbations with system identification techniques to detect such asymmetries in balance control of two patients with Parkinson's disease. Results were compared to those of six healthy controls. Our pilot data show clear asymmetries in dynamic balance control, even though patients themselves were not aware of this and had no subjective problems with stability or standing. We also found asymmetries in weight bearing, but the asymmetries in dynamic balance contribution were larger. Finally, asymmetries in weight bearing and dynamic balance in patients were not tightly coupled as in healthy controls. Future studies could incorporate this approach when examining the influence of mental decline on postural regulation.
Journal of Neural Transmission 02/2007; 114(10):1333-7. · 3.05 Impact Factor