A pilot study on the motor effects of rimantadine in Parkinson's disease

The purpose of this pilot study was to determine whether rimantadine, the alpha-methyl derivative of amantadine, might have any antiparkinsonian properties. In an open-label trial, 14 patients (12 de novo and 2 on levodopa treatment) with Hoehn and Yahr stage 2 to 3 Parkinson's disease were placed on rimantadine at doses of 100 to 300 mg/d. No patients had dyskinesias or motor fluctuations. Ten of 14 (71%) reported a mean subjective response of 33% (range 10%-60%) to rimantadine. After treatment, there was a 13% improvement in Hoehn and Yahr staging (p = .01) and a 20% improvement in mean motor Unified Parkinsons Disease Rating Scale scores (p = .02). Rigidity was the most consistently improved feature among the responders. Mean effective dose was 256 mg/d (range 200-300 mg/d). Side effects were mild and transient, with nausea being most common (4/14). We conclude that rimantadine has some motor benefits in Parkinson's disease. A double-blind placebo-controlled study is warranted to validate our findings.     

A pilot study of risk factors for dementia in Parkinson's disease

To determine whether the risk factors for dementia in idiopathic Parkinson's disease (IPD) are similar to the risk factors for Alzheimer's disease, we conducted a case-control study of potential risk factors. A structured interview was administered to surrogates of 17 demented subjects with IPD and 54 nondemented subjects. Two factors emerged as possible risks for dementia. Demented patients were older than nondemented patients, although the duration of symptoms was similar. A family history of dementia was present in 30% of the demented group and 5.6% of the nondemented group. Dementia was most often reported among siblings. No difference was seen in toxic and occupational exposure, personal habits, or medical or surgical illnesses. We conclude that dementia in IPD shares some common risk factors with Alzheimer's disease. Efforts to assess the contribution of genetic susceptibility or shared environmental influences may clarify the relationship between these two diseases.     

Abnormal bone and calcium metabolism in immobilized Parkinson's disease patients.

To elucidate the influence of immobilization-induced hypercalcemia on bone metabolism in Parkinson's disease (PD), we measured serum biochemical indexes and bone mineral density (BMD) in the second metacarpals of 142 elderly PD patients and 99 age-matched healthy controls. Serum concentrations of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-[OH](2)D), ionized calcium, intact parathyroid hormone (PTH), and intact bone Gla protein (BGP) were measured. Urinary deoxypyridinoline (D-Pyr) was also measured. Increased serum calcium levels (mean, 1.27 mmol/L) were observed in PD patients, and the levels correlated negatively with the Unified Parkinson's Disease Rating Scale III (UPDRS III), indicating the presence of immobilization-induced bone resorption with resultant hypercalcemia. Decreased serum concentrations of 1,25-[OH](2)D (mean, 88.7 pmol/L) and 25-OHD (mean, 29.7 nmol/L) were noted. Serum PTH was decreased (mean, 25.2 ng/L). Serum BGP was decreased while urinary D-Pyr concentration elevated. A negative correlation was observed between 1,25-[OH](2)D levels and serum calcium or UPDRS III (P < 0.0001). In disabled PD patients, immobilization-induced hypercalcemia may inhibit secretion of PTH, which in turn suppresses 1,25-[OH](2)D production. 25-OHD insufficiency may also contribute to decreased 1,25-[OH](2)D. These abnormalities may be corrected by the suppression of bone resorption with bisphoshonate, and supplementations of calcium and vitamin D should be avoided in these patients.     

Impairments of speed and amplitude of movement in Parkinson's disease: A pilot study

Bradykinesia, characterized by slowness and decreased amplitude of movement, is often considered the most important deficit in Parkinson's disease (PD). The current clinical rating of bradykinesia in PD, based on the motor subscale of the Unified Parkinson's disease Rating Scale (UPDRS‐III), does not individually weigh the impairments in speed and amplitude of rapid alternating movements. We sought to categorize movement in PD to determine whether speed and amplitude have different relationships to current measures of motor impairment and disability. Categories of speed and amplitude (normal, slow/low, and very‐slow/very‐low) were ascertained using an electromagnetic tracking device. Amplitude was disproportionally more affected than speed in the “off” state. UPDRS‐III and the Schwab & England disability scale were worst in patients with very impaired amplitude and best in patients with normal amplitude. A similarly graded relationship was not found for categories of speed impairment. The examiner clinical global impression of change mirrored “off” state amplitude but not speed categories. Levodopa, however, normalized speed to a greater extent than amplitude. Our observations suggest that amplitude and speed impairments may be associated with different functional aspects in PD and deserve separate clinical assessment. © 2009 Movement Disorder Society     

A computerized survey of pain in Parkinson's disease patients: A pilot feasibility study

Approximately two thirds of Parkinson's disease (PD) patients exhibit bothersome pain symptoms that oftentimes go unrecognized. In this study, 14 patients with PD volunteered to complete a computerized version of the McGill Pain Questionnaire using the PAINReportIt^® interactive software to assess the feasibility of acquiring real-time pain data in a clinical setting. 100% of the subjects completed >90% of questions in an average of 19.9 min; however, some subjects (n = 4, 28.6%) required physical assistance. 92.9% (n = 13) of subjects supported use of PAINReportIt^® across all measures. PAINReportIt^® was feasible as a data-collection modality among our PD cohort, and with modifications may be used as both an investigative instrument and clinical tool for the evaluation of PD-related pain syndromes.     

Tolerability of isradipine in early Parkinson's disease: A pilot dose escalation study

Recent data suggests that isradipine, a dihydropyridine calcium channel blocker, is neuroprotective in preclinical models of parkinsonism. Isradipine has not been systematically studied in patients with Parkinson's disease (PD). The aim of this study was to evaluate safety and tolerability of isradipine controlled release (CR) in patients with early PD. Qualified subjects (n = 31) received isradipine CR, titrated from 5 to 20 mg daily dose over 8 weeks as tolerated. Eighty‐one percent of subjects completed the study. Tolerability of isradipine CR was dose dependent: 94% for 5 mg dose; 87% for 10 mg; 68% for 15 mg; and 52% for 20 mg. Isradipine had no significant effect on blood pressure or PD motor disability. The two most common reasons for dose reduction were leg edema (7) and dizziness (3). There was no difference in isradipine tolerability between subjects with and without dopaminergic treatment, or with and without hypertension. © 2010 Movement Disorder Society     

A pilot study of occupational and environmental risk factors for Parkinson's disease.

Increasingly, the etiology of Parkinson's disease (PD) has been linked to exposures to environmental toxicants. This epidemiologic pilot study used a self-administered questionnaire among 34 PD cases and 22 other neurology clinic control patients. All subjects were at least 40 years old. Risk factors investigated included occupation, well-water use, pesticide use, metal exposures, medical history, smoking, alcohol consumption, and drug use. Twenty-six percent of the male PD cases reported having been employed in farming versus eleven percent for male controls (OR = 3.1, 95% C.I. = 0.3 to 35). Sixteen percent of male cases versus none of the controls reported employment as welders. No clear trends involving exposure to either occupational or home pesticides emerged. In assessing occupational exposures to metals, aluminum and copper exposures tended to be more common among male cases than male controls. Additionally, as reported in other studies, smoking showed an inverse relationship with PD. Although the findings reported here are provocative, these results are statistically imprecise and must be interpreted cautiously because of the small number of subjects included in the study.     

Treatment of depression in Parkinson's disease with moclobemide: A pilot open-label study

Moclobemide, a potent reversible monoamine-oxidase A (MAO-A) inhibitor, is an effective antidepressant that does not cause impairment of cognitive function in elderly patients and might be beneficial to motor deficits in Parkinson's disease (PD). In a 12-week open-label prospective study, we administered moclobemide (300–600 mg day⁻¹) as an add-on medication to twelve PD patients who met DSM-III-R criteria for depressive illness. There were two early drop-outs due to subjective worsening of Parkinsonism associated with insomnia and anorexia, respectively. The Beck Depression Inventory score decreased significantly in the ten patients who completed the study, and clinical global assessment of efficacy recorded ‘good’ or ‘excellent’ responses or in nine of the ten patients. Mean parkinsonian disability, as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and Schwab-England Daily Life Activities scales, remained unchanged throughout the study in the group as a whole. However, worsening or onset of resting tremor occurred in five patients and the UPDRS tremor subscore in the group overall was significantly higher by week 8 (p = 0.03) when dose titration was optimal. There was a trend toward improvement in UPDRS bradykinesia subscores that did not attain statistical significance. Compared to baseline, patients complained more often of insomnia, anorexia, increased perspiration, and restlessness. Though these preliminary results need to be replicated in a large controlled trial, we suggest that moclobemide may be an effective alternative in the treatment of PD associated depression.     

cGMP level in idiopathic Parkinson's disease patients with and without cardiovascular disease - A pilot study

We have previously found that average serum cGMP level in unselected patients with Parkinson’s disease (PD), particularly in patients treated with a combination of l-DOPA and the dopamine agonist pergolide mesylate, is markedly higher than that in healthy controls. Here we compared serum cGMP and total testosterone levels between l-DOPA/pergolide mesylate-treated male idiopathic PD patients without and with cardiovascular disease (iPD, n = 10, and iPD-CVD, n = 10, respectively) and age-matched healthy volunteers (n = 10). There was no difference in PD-related disability between the two patient groups as assessed by UPDRS motor score and Hoehn-Yahr staging. Whereas none of the patients showed hypoandrogenemia, PD patients compared to controls revealed significantly lower serum testosterone levels, and iPD-CVD patients showed significantly lower levels than iPD patients. Serum cGMP levels were but moderately while significantly higher in the two groups of PD patients than in the controls, and were the highest in the iPD-CVD group. For all study groups combined, there was a high negative correlation between total testosterone level and cGMP level. Our data indicate that blood total testosterone level is negatively correlated with general health status in PD patients, whereas the reverse is true for blood cGMP level.     

Effect of whole body vibration in Parkinson's disease: A controlled study

In the search of new strategies to improve the quality of life of Parkinson's disease patients, recent work has reported an amelioration of Parkinsonian symptoms using Whole Body Vibration (WBV). A double‐blinded, placebo controlled design was used to evaluate the effect of a 12 WBV sessions‐programme on a number of motor and clinical tests in 23 Parkinson's disease patients. Patients were assigned to one of two groups, one receiving WBV and the other a placebo group. At the end of the programme as well as during intra‐session evaluation, there was no difference between the experimental (vibration) and placebo groups in any outcomes. These results suggest that reported benefits of vibration are due to a placebo response. © 2009 Movement Disorder Society     

Testosterone deficiency and apathy in Parkinson's disease: a pilot study

BACKGROUND: Low testosterone in men with Parkinson's disease may be associated with non-motor symptoms of the disease, such as apathy. OBJECTIVE: To determine the association between free serum testosterone level and apathy in elderly men with Parkinson's disease. METHODS: Consecutive non-demented patients (n = 49) and knowledgeable informants (n = 40) participated in the study. Patients and informants reported on apathy using the Frontal Systems Behavior Scale and two visual analogue scales. Patients also provided self reported symptoms of depression on the Beck depression inventory-II. Blood samples were drawn at the time of assessment to determine testosterone levels. RESULTS: A low total testosterone concentration was found in 46.9% of the patients, defined as < or = 325 ng/dl. Free testosterone was significantly correlated with both patient reported and informant reported apathy, independent of disease severity. CONCLUSIONS: Apathy is common in Parkinson's disease and is inversely correlated with free testosterone. Testosterone replacement therapy could be considered as a potential treatment for apathy in some men with Parkinson's disease. More research is needed to replicate these findings and to investigate the response to treatment.     

Ethosuximide and tremor in Parkinson's disease: a pilot study.

Following the demonstration of an anti-tremor effect of ethosuximide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model, we have tested the effect of this drug in 10 patients with typical parkinsonian tremor. Six patients suffered from Parkinson's disease with prominent, relatively drug-resistant rest tremor. The other four patients had a drug-induced parkinsonian tremor due to neuroleptic agents taken for a psychiatric condition. Five of the six parkinsonian patients and three of the four psychiatric patients reported within a few days a marked and intolerable exacerbation of their tremor. One patient in each group was improved, and this improvement was verified in repeated examinations. Thus, for unknown reasons, the effect of ethosuximide was not as predicted by the monkey model. Among possible explanations is the fact that we had chosen patients with drug-resistant tremor.     

Carbamazepine and bone mineral metabolism

The status of bone mineral metabolism was studied in 21 epileptic out-patients receiving carbamazepine as the sole anticonvulsant drug. Hypocalcaemia was found in 3, hypophosphataemia in one and elevated serum alkaline phosphatase in 4 of the cases. Serum 25-hydroxyvitamin D values were significantly lower in the patients than in the controls. No statistically significant difference was observed in bone mineral density between the patients and controls. Histomorphometric analysis of the iliac crest cancellous bone did not reveal any statistically significant difference in the amount of trabecular bone or osteoid between the patients and controls, but the patients had an increased amount of trabecular resorption surfaces. An increased amount of osteoid, suggesting histological osteomalacia, was found in 2 of the 18 biopsies. We conclude that epileptic out-patients receiving carbamazepine therapy have vitamin D deficiency and may develop osteomalacic changes in their skeleton.     

A 2-year prospective study of bone metabolism and bone mineral density in adolescents with anorexia nervosa

Summary Osteopenia and osteoporosis are complications of adolescent anorexia nervosa (AN) and may result in a permanent deficit of bone mass in adulthood. It is still unclear if a complete catch-up in bone mineral density (BMD) is possible after weight rehabilitation in AN. Methods. We investigated bone formation (bAP, PICP), bone resorption (CTX) and BMD (lumbar spine, femoral neck) along with endocrinological parameters in 19 girls with AN (14.4 ± 1.6 years) and in 19 healthy controls for 2 years after inpatient re-feeding. Results. Re-feeding normalised bone formation activity in patients. The pattern of bone turnover in patients after 2 years was similar to the pattern healthy controls had shown 2 years before. BMD of patients was significantly lower than in controls and did not change throughout the entire study. Conclusions. Weight rehabilitation leads to prolonged normalization of bone turnover in adolescent AN. Since we could not observe a “catch up” effect in BMD of girls with AN in a 2-year follow-up, BMD of these patients needs to be carefully monitored until adulthood to detect early osteoporosis. The first two authors contributed equally     

The treatment of diffuse lewy body disease: A pilot study

Single case studies may provide useful information and generate hypotheses for later testing in group studies. The effect of anti-Parkinsonian medication is reported in five individual cases of diffuse Lewy body disease. The problems caused by the variability in congnitive function and psychiatric symptoms in these cases are outlined together with suggested strategies for future research.     

Effects of movement imitation training in Parkinson's disease: A virtual reality pilot study

BackgroundHypometria is a clinical motor sign in Parkinson's disease. Its origin likely emerges from basal ganglia dysfunction, leading to an impaired control of inhibitory intracortical motor circuits. Some neurorehabilitation approaches include movement imitation training; besides the effects of motor practice, there might be a benefit due to observation and imitation of un-altered movement patterns. In this sense, virtual reality facilitates the process by customizing motor-patterns to be observed and imitated.ObjectiveTo evaluate the effect of a motor-imitation therapy focused on hypometria in Parkinson's disease using virtual reality.MethodsWe carried out a randomized controlled pilot-study. Sixteen patients were randomly assigned in experimental and control groups. Groups underwent 4-weeks of training based on finger-tapping with the dominant hand, in which imitation was the differential factor (only the experimental group imitated). We evaluated self-paced movement features and cortico-spinal excitability (recruitment curves and silent periods in both hemispheres) before, immediately after, and two weeks after the training period.ResultsMovement amplitude increased significantly after the therapy in the experimental group for the trained and un-trained hands. Motor thresholds and silent periods evaluated with transcranial magnetic stimulation were differently modified by training in the two groups; although the changes in the input–output recruitment were similar.ConclusionsThis pilot study suggests that movement imitation therapy enhances the effect of motor practice in patients with Parkinson's disease; imitation-training might be helpful for reducing hypometria in these patients. These results must be clarified in future larger trials.