Motor Function In Parkinson's Disease Research Articles

Vibration Therapy for Parkinson's Disease: Charcot's Studies Revisited

The 19th century neurologist, J-M Charcot, used a vibration chair for treating Parkinson's disease (PD). He documented improvement, but few subsequent studies examined vibration treatment. Using a specialized lounge chair, we conducted a rater blinded, randomized trial of body vibration vs. no vibration in 23 PD patients. The primary outcome measure was change from baseline in the motor section of the MDS-UPDRS. Both vibration and no vibration groups significantly improved after one month of daily treatments. However, there was no significant difference between the two treatment groups, suggesting that non-specific or placebo factors had an effect on PD motor function.

Brief Cognitive Assessment in the Early Stages of Parkinson Disease

Cognitive dysfunction is an integral part of the Parkinson disease (PD) symptom spectrum. Early detection of cognitive dysfunction could help to delineate prevention strategies. Our main objective was to study the validity of brief cognitive tests, the Frontal Assessment Battery (FAB) and Mini-Mental State Examination (MMSE), as cognitive screening tools for detecting global and executive cognitive deficits in early stages of PD, as compared to a healthy control population. We evaluated 75 early-stage PD patients and 45 healthy age-matched and education-matched controls with the MMSE (global test) and FAB (frontal test), and compared total and subtest scores. We evaluated PD motor function with the Unified Parkinson Disease Rating Scale Part III. We assessed the relationship between cognitive and motor variables. Frontal and global cognitive dysfunction was significantly more frequent in PD patients. PD patients scored significantly lower on FAB total and similarities, motor series, and conflicting instructions scores, and on the MMSE total, visuoconstructive, and memory scores. MMSE scores correlated significantly with Unified Parkinson Disease Rating Scale part III total score, speech, and bradykinesia scores. Early-stage PD patients present with frontal, memory, and visuoconstructive deficits in brief cognitive tests. Our results suggest that these brief bedside tests are useful for cognitive deficit screening in the early stages of PD. Our study did not account for the influence of depression in cognition. This constitutes a limitation, because many PD patients have depressive symptoms, which some studies have shown can be related to cognitive dysfunction.

Is the loss of thalamostriatal neurons protective in parkinsonism?

Neuronal loss in Parkinson's disease (PD) is more widespread than originally thought. Among the extrastriatal sites in which significant loss of neurons has been reported is the centremedian-parafascicular (CM-PF) complex of the thalamus, which provides one of the three major afferent sources to the striatum. The functional significance of CM-PF loss in PD is unclear. Interestingly, several recent small trials have suggested that deep brain stimulation of the CM-PF improves motor function in PD. We discuss the possible transsynaptic determination of CM-PF loss secondary to nigrostriatal dopamine degeneration, and suggest that expression of the glycoprotein cerebellin1 (Cbln1) in CM-PF neurons may play an important role in striatal synaptic remodeling in parkinsonism.

Proprioception and Motor Control in Parkinson's Disease

ABSTRACT Parkinson's disease (PD) is a neurodegenerative disorder that leads to a progressive decline in motor function. Growing evidence indicates that PD patients also experience an array of sensory problems that negatively impact motor function. This is especially true for proprioceptive deficits, which profoundly degrade motor performance. This review specifically address the relation between proprioception and motor impairments in PD. It is structured around 4 themes: (a) It examines whether the sensitivity of kinaesthetic perception, which is based on proprioceptive inputs, is actually altered in PD. (b) It discusses whether failed processes of proprioceptive-motor integration are central to the motor problems in PD. (c) It presents recent findings focusing on the link between the proprioception and the balance problems in PD. And (d) it discusses the current state of knowledge of how levodopa medication and deep brain stimulation affect proprioceptive and motor function in PD. The authors conclude that a failure to evaluate and to map proprioceptive information onto voluntary and reflexive motor commands is an integral part of the observed motor symptoms in PD.

Role of an electronic armband in motor function monitoring in patients with Parkinson's disease

Objective Levodopa replacement still is the gold standard for the management of Parkinson's disease (PD). Long-term treatment with levodopa is frequently associated with motor fluctuations. A low-protein (LP) dietary regimen has proved to be effective in reducing this adverse effect, but has been associated with weight loss, probably due to increased energy expenditure. A new wearable device (SenseWear Armband [SWA]) has recently been introduced into clinical practice. It is designed to monitor physical activity continuously and provide estimates of energy consumption. We assessed its role in measuring the effects of dietary regimens on motor function in PD. Methods Six patients with levodopa-treated PD and motor fluctuations were asked to follow a balanced diet (protein 1 g · kg −1 · d −1) for 7 d and then to cross over to a isocaloric LP (protein 0.7 g · kg −1 · d −1) dietary regimen. Total daily energy expenditures, physical activity, number of steps, and metabolic rate were assessed continuously (14 d) by the SWA. Motor control was evaluated by daily diaries. Results The SWA proved that, during the LP diet, mean total daily energy expenditure was higher ( P < 0.05) and so were physical activity ( P = 0.05) and average metabolic rate ( P = 0.01), despite no change in the number of steps. The duration of periods with dyskinesias was also increased ( P < 0.05). These data support the role of upper-extremity involuntary movements in increasing total daily energy expenditure during an LP diet. Conclusion The SWA may help in monitoring patients with PD because it can assist in evaluating motor response to treatment and changes in physical activity and daily calorie needs.

Effects of acute tryptophan depletion on neuropsychological and motor function in Parkinson’s disease

Interactions between the 5-HT system and the dopaminergic system and cholinergic system may be important in determining cognitive function and motor function in Parkinson's disease (PD). Previous studies have shown effects of reducing serotonin function, by acute tryptophan depletion (ATD), on neuropsychological function. In particular, an adverse effect on verbal memory has been demonstrated. This study compared with the effects of ATD on cognitive and motor function in PD and healthy control subjects. The effects of ATD were investigated in a double-blind, placebo-controlled, counterbalanced, cross-over, randomised design in 20 patients with PD and 35 healthy controls matched for age, gender and premorbid IQ. There was a differential group effect of ATD on global cognitive function whereby the mean score on the modified mini mental state examination during ATD was lower than placebo in PD but higher in controls. There was a similar pattern of effects on verbal recognition. In a visual recognition task, ATD improved performance in the PD but not in the control group. In terms of psychomotor speed, there was also a group-specific effect with reduced latency of response during ATD in the PD group but increased latency in the control group. ATD has subtle neuropsychological effects, which differ significantly between PD and healthy control subjects. This suggests that the dopaminergic and cholinergic deficit of PD significantly modulates the effects of serotonin depletion, resulting in positive effects in some domains. Further investigation on the effects of specific serotonin antagonists may be merited in PD.

Foot-Tapping Rate as an Objective Outcome Measure for Parkinson Disease Clinical Trials

To explore foot-tapping rate as a reliable and a valid measure of motor function in Parkinson disease (PD). We present data from a randomized, single-blind, outpatient study and a randomized, double-blind, placebo-controlled, crossover, inpatient study. Fifty PD subjects completed the outpatient study. A Unified Parkinson Disease Rating Scale motor score was determined for each subject. Subsequently, finger tapping, alternate (between 2 pedals) and repetitive (on 1 pedal) foot-tapping rates, and gait were measured. Thirteen PD subjects completed the inpatient study. Each subject received a daily infusion of high-dose apomorphine (APO), low-dose APO, and placebo in random order over 3 days. In this subanalysis, we compared variance and reliability of the finger- and the foot-tapping techniques during the placebo day and compared the validity of these outcome measures to detect improvement in parkinsonism during high-dose APO infusion. Alternate foot tapping was reliable (interclass correlation on the placebo inpatient day, 84%). Only foot tapping detected improvement in parkinsonism with high-dose APO treatment (a measure of validity). In the outpatient study, there was a significant correlation between alternate and repetitive tapping with finger tapping (R2 = 0.28 and 0.23, respectively) and Unified Parkinson Disease Rating Scale motor score (R2 = 0.09 and 0.08), but only alternate tapping correlated with gait (R2 = 0.16). Alternate foot tapping was equally reliable but more valid than finger tapping. Alternate foot tapping correlated better did existing PD outcome measures than did repetitive foot tapping. Foot tapping may be a useful outcome measure for determination of dopaminergic medication effect in PD clinical trials.

Forced-exercise Improves Motor Function In Parkinson's Disease Patients

Despite promising results in animal models of Parkinson's disease (PD), human studies describe limited and short-term improvements in motor function following exercise. These discrepancies may be due to differences in exercise rate or modality. The hypothesis underlying this project is that PD patients lack the capacity to exercise at a voluntary rate necessary to alter central nervous system functioning and promote maximal symptom relief. PURPOSE: To determine the effects of voluntary compared to forced-exercise on PD motor function. METHODS: Ten PD patients were randomized to either a voluntary or forcedexercise group. Workload and heart rate was similar between groups, while exercise rate was manipulated. The forced-exercise group cycled on a stationary tandem bicycle for 8 weeks with an able-bodied trainer at a cadence of 80-90 revolutions per minute. Patients were 'forced' to pedal at a cadence greater than their voluntary cadence as their pedals are mechanically linked to those of the trainer. Patients in the voluntary group exercised on a stationary cycle and were not given instructions regarding cadence. Clinical motor function tests were used to assess overall motor function and a bimanual dexterity paradigm was used to assess hand function. RESULTS: Both groups displayed improvements in aerobic fitness. Clinical ratings of motor function showed significant improvement, 35%, for patients in the forced-exercise group compared to no change in the voluntary group. Bimanual dexterity also improved for the forced-exercise group while no change in function was observed for the voluntary group. CONCLUSIONS: These results indicate that increasing exercise rate in PD patients, beyond a self-selected rate, leads to improvements in motor function compared to voluntary exercise. Improved bimanual dexterity following forced-exercise suggests a fundamental shift in the control and coordination of upper extremity actions. Improvements in upper extremity motor function following a lower extremity forced-exercise intervention provide evidence for a change in central nervous system functioning. These findings are consistent with the recent animal literature. Overall, our data indicate that forced-exercise leads to improvements in motor functioning and may be a viable intervention for PD patients.

Unilateral subthalamic nucleus stimulation has a measurable ipsilateral effect on rigidity and bradykinesia in parkinson disease

Background Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor function in Parkinson disease (PD). However, little is known about the quantitative effects on motor behavior of unilateral STN DBS. Methods In 52 PD subjects with STN DBS, we quantified in a double-blinded manner rigidity ( n = 42), bradykinesia ( n = 38), and gait speed ( n = 45). Subjects were tested in four DBS conditions: both on, left on, right on and both off. A force transducer was used to measure rigidity across the elbow, and gyroscopes were used to measure angular velocity of hand rotations for bradykinesia. About half of the subjects were rated using the Unified Parkinson Disease Rating Scale (part III) motor scores for arm rigidity and repetitive hand rotation simultaneously during the kinematic measurements. Subjects were timed walking 25 feet. Results All subjects had significant improvement with bilateral STN DBS. Contralateral, ipsilateral and bilateral stimulation significantly reduced rigidity and bradykinesia. Bilateral stimulation improved rigidity more than unilateral stimulation of either side, but there was no significant difference between ipsilateral and contralateral stimulation. Although bilateral stimulation also increased hand rotation velocity more than unilateral stimulation of either side, contralateral stimulation increased hand rotation significantly more than ipsilateral stimulation. All stimulation conditions improved walking time but bilateral stimulation provided the greatest improvement. Conclusions Unilateral STN DBS decreased rigidity and bradykinesia contralaterally as well ipsilaterally. As expected, bilateral DBS improved gait more than unilateral DBS.

Unilateral vs. bilateral STN DBS effects on working memory and motor function in Parkinson disease

Bilateral subthalamic nucleus deep brain stimulation (STN DBS) can reduce working memory while improving motor function in Parkinson disease (PD), but findings are variable. One possible explanation for this variability is that the effects of bilateral STN DBS on working memory function depend in part on functional or disease asymmetry. The goal of this study was to determine the relative contributions of unilateral DBS to the effects seen with bilateral DBS. Motor (Unified Parkinson Disease Rating Scale Part III, UPDRS) and working memory function (Spatial Delayed Response, SDR) were measured in 49 PD patients with bilateral STN DBS while stimulators were Both-off, Left-on, Right-on and Both-on in a randomized, double-blind manner. Patients were off PD medications overnight. Effects of unilateral DBS were compared to effects of bilateral STN DBS. Mean UPDRS and SDR responses to Left-on vs. Right-on conditions did not differ ( p > .20). However, improvement in contralateral UPDRS was greater and SDR performance was more impaired by unilateral DBS in the more affected side of the brain than in the less affected side of the brain ( p = .008). The effect of unilateral DBS on the more affected side on contralateral UPDRS and SDR responses was equivalent to that of bilateral DBS. These results suggest that motor and working memory function respond to unilateral STN DBS differentially depending on the asymmetry of motor symptoms.

Zonisamide improves motor function in Parkinson disease: A randomized, double-blind study

In the article “Zonisamide improves motor function in Parkinson disease: A randomized, double-blind study” by …

Practice Parameter: Neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology

Objective: To define key issues in the management of Parkinson disease (PD) relating to neuroprotective strategies and alternative treatments, and to make evidence-based treatment recommendations. Methods: Two clinical questions were identified. 1) In a patient diagnosed with PD, are there any therapies that can slow disease progression? 2) Are there any nonstandard pharmacologic or nonpharmacologic therapies that have been shown to improve motor function in PD? Articles were classified according to a four-tiered level of evidence scheme. Recommendations were based on the evidence. Results and conclusions: 1. Levodopa does not appear to accelerate disease progression. 2. No treatment has been shown to be neuroprotective. 3. There is no evidence that vitamin or food additives can improve motor function in PD. 4. Exercise may be helpful in improving motor function. 5. Speech therapy may be helpful in improving speech volume. 6. No manual therapy has been shown to be helpful in the treatment of motor symptoms, although studies in this area are limited. Further studies using a rigorous scientific method are needed to determine efficacy of alternative therapies.

Zonisamide improves motor function in Parkinson disease

To evaluate the efficacy, safety and tolerability of daily doses of 25, 50, and 100 mg of zonisamide (ZNS) administered as adjunctive treatment in patients with Parkinson disease (PD). We conducted a multicenter, randomized, double-blind, parallel-treatment, placebo-controlled study in Japan. Patients with PD who showed insufficient response to levodopa treatment were given placebo for 2 weeks and then treated for 12 weeks with 25, 50, or 100 mg/day of ZNS or placebo, in addition to levodopa, followed by a 2-week dose-reduction period. The primary endpoint was change from baseline in the total score of the Unified Parkinson's Disease Rating Scale (UPDRS) Part III at the final assessment point. Secondary endpoints included changes from baseline in total daily "off" time; total scores of UPDRS Parts I, II, and IV; and Modified Hoehn and Yahr Scale score. Safety analysis was based on the incidence of adverse events. There was significant improvement in the primary endpoint in the 25-mg and 50-mg groups vs placebo. The duration of "off" time was significantly reduced in the 50-mg and 100-mg groups vs placebo. Dyskinesia was not increased in ZNS groups. The incidence of adverse effects was similar between the 25-mg, 50-mg, and placebo groups but higher in the 100-mg group. Zonisamide is safe, effective and well tolerated at 25 to 100 mg/day as an adjunctive treatment in patients with Parkinson disease.

Practice Parameter: Neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): [RETIRED

To define key issues in the management of Parkinson disease (PD) relating to neuroprotective strategies and alternative treatments, and to make evidence-based treatment recommendations. Two clinical questions were identified. 1) In a patient diagnosed with PD, are there any therapies that can slow disease progression? 2) Are there any nonstandard pharmacologic or nonpharmacologic therapies that have been shown to improve motor function in PD? Articles were classified according to a four-tiered level of evidence scheme. Recommendations were based on the evidence. 1. Levodopa does not appear to accelerate disease progression. 2. No treatment has been shown to be neuroprotective. 3. There is no evidence that vitamin or food additives can improve motor function in PD. 4. Exercise may be helpful in improving motor function. 5. Speech therapy may be helpful in improving speech volume. 6. No manual therapy has been shown to be helpful in the treatment of motor symptoms, although studies in this area are limited. Further studies using a rigorous scientific method are needed to determine efficacy of alternative therapies.

Depression is associated with impairment of ADL, not motor function in Parkinson disease

We read the Holroyd et al. article with great interest.1 We evaluated 50 patients with Parkinson disease (PD). All patients had idiopathic PD, none had a previous history of stroke, and all met Diagnostic and Statistical Manual of Mental Disorders–III criteria for dementia. We evaluated depressive state using Zung self- rating depression scale.2 Motor disability (tremor, rigidity, bradykinesia), Hoehn & Yahr stage, age at onset, levodopa dosage, duration of illness, history of depression, and score on Mini-Mental State Examination3 did not correlate with the SDS …

The 57th Annual Meeting of the American Academy of Neurology, Miami, Florida, April 9-16, 2005

The 57th Annual Meeting of the American Academy of Neurology, Miami, Florida, April 9-16, 2005

Depression is associated with impairment of ADL, not motor function in Parkinson disease

Depression was diagnosed in 15% of 100 consecutive patients with Parkinson disease (PD). Depression was associated with lower cognition, history of depression, and a higher Unified Parkinson's Disease Rating Scale score. The latter was due to differences in the activities of daily living (ADL) subscale (17 +/- 7 vs 12 +/- 6; p = 0.004) rather than the motor subscale (30 +/- 13 vs 26 +/- 13; p = 0.27). These results suggest that ADL impairment may in part be due to depression. Patients with PD with poor function should be closely evaluated for depression.

Response to levodopa treatment in dopa-responsive dystonia.

Dopa-responsive dystonia (DRD) is similar to Parkinson disease in that both disorders have impaired dopamine synthesis and respond to levodopa treatment. Dopa-responsive dystonia differs in that dopamine storage is intact in contrast to Parkinson disease in which it is markedly reduced. To examine the short- and long-duration responses to levodopa dosing in subjects with DRD. The response to brief infusions of levodopa was examined in 4 subjects with DRD and the effects of withdrawal of levodopa for 3 to 7 days studied in the 3 subjects receiving long-term levodopa therapy. Motor function was measured with tapping speed, Unified Parkinson's Disease Rating Scale motor score, and global dystonia score. The short-duration response to levodopa dosing seems to develop more slowly and persists longer in subjects with DRD than in subjects with Parkinson disease. Withdrawal of levodopa leads to a gradual decline in tapping speed and reemergence of dystonia over several days, similar to the rate of decay of motor function in Parkinson disease. The short- and long-duration responses were not clearly differentiated in DRD. This pilot study suggests that retained dopamine storage in DRD may prolong the short-duration response and blur the distinction of the short- and long-duration responses. The decline in motor function in DRD on withdrawal of long-term levodopa therapy resembles that in Parkinson disease, suggesting that a long-duration response, if it exists in DRD, is unrelated to dopamine storage.