Dopaminergic effects on the implicit processing of distractor objects in Parkinson's disease.

The aim of the present study was to assess the effects of dopaminergic medication on the selection-for-action mechanisms in Parkinson's disease (PD). PD subjects were tested after not having taken medication for at least 12 h ("Off' state) and then retested 1-2 h after medication ("On" state). A three-dimensional kinematic system (ELITE, BTS, Italy) was used to record reach-to-grasp movements to a target object placed at a reaching distance of 30 cm. The target was presented alone or in the presence of distractor objects, which could be of either the same size (compatible distractor) or a different size (incompatible distractor). PD subjects in the Off state were significantly more affected by the presence of the incompatible distractor than in the On state. These results indicate that dopaminergic medication is of benefit in reducing interference effects when distractor objects evoke motor programs that differ from the motor program elicited by the target. Results are discussed in light of the role played by the striatal and mesocortical dopaminergic systems for response selection in basal ganglia disorders.

The reach-to-grasp movement in Parkinson's disease before and after dopaminergic medication.

The aim of the present study was to assess the effects of dopaminergic medication on the organisation of the reach-to-grasp movement in Parkinson's disease. A three-dimensional kinematic system (ELITE, B/T/S Italy) was used to record reach-to-grasp movements to objects of either small (0.7 cm) or large (8 cm) diameter placed at a reaching distance of either 20 or 30 cm. Vision of the reaching limb and target was also manipulated. Parkinson's disease participants (N = 14) were assessed in 'OFF' (12 h without medication) and 'ON' (1-2 h post-administration of medication) states. In the 'ON' state, movement duration and the time spent in arm deceleration were significantly less than in the 'OFF' state. The amplitudes of peak reaching velocity, acceleration and deceleration were all higher in the 'ON' than in the 'OFF' state. Further, in the 'ON' state, the acceleration profile no longer exhibited small irregular adjustments, the number of significant correlations between parameters measured from the transport and manipulation components was greater, and the movement was more direct in both the mediolateral horizontal and vertical planes. These results indicate that dopaminergic medication is of benefit in reducing bradykinesia and in fine-tuning kinematic parameterisation of a selected reach-to-grasp action.

The reach-to-grasp movement in Parkinson's disease: response to a simultaneous perturbation of object position and object size.

This study assessed the adaptive response of the reach-to-grasp movement of 12 Parkinson's disease (PD) and 12 control subjects to a simultaneous perturbation of target object location and size. The main aim was to test further the reported dysfunction of PD subjects in the simultaneous activation of movement components. Participants were required to reach 30 cm to grasp a central illuminated cylinder of either small (0.7 cm) or large (8 cm) diameter. For a small percentage of trials (20/100) a visual perturbation was introduced unexpectedly at the onset of the reaching action. This consisted of a shift of illumination from the central cylinder to a cylinder of differing diameter, which was positioned 20 degrees to the left (n = 10) or to the right (n = 10). The subject was required to grasp the newly illuminated cylinder. For the Parkinson's disease subject group, the earliest response to this 'double' perturbation was in the parameter of peak reaching acceleration, which was on average 50 ms earlier for 'double' perturbed than for non-perturbed trials. The grasp component response followed more than 500 ms after the earliest transport response. For the control subjects initial signs of a response to the 'double' perturbation were seen almost simultaneously in the transport parameter of peak arm deceleration, and in the manipulation parameter of maximum grip aperture, but these changes were not evident until more than 400 ms after movement onset. These results indicate that the basal ganglia can be identified as part of a circuit which is involved in the integration of parallel neutral pathways, and which exercise flexibility in the degree to which these components are 'coupled' functionally. With basal ganglia dysfunction the activation of integration centres that at first gate the flow of information to the parallel channels of reach and grasp seems inefficient.

The effect of unilateral posteroventral pallidotomy on the kinematics of the reach to grasp movement.

OBJECTIVE: To assess postoperative effects of unilateral posteroventral pallidotomy on the organisation of upper limb movement. METHODS: A three dimensional kinematic system (ELITE, B/T/S/ Italy) was used to record reach to grasp movements to objects of either small (0.7 cm) or large (8 cm) diameter placed at a reaching distance of either 20 or 30 cm. Four patients with Parkinson's disease were assessed in "off" (12 hours without medication) and "on" (1 hour after administration of medication) preoperatively and postoperatively. RESULTS: Duration of the movement and the time spent in arm deceleration were significantly reduced after surgery. However, movement patterning according to object size was adversely affected. Postoperatively, all four patients showed an abnormal pattern of a longer movement duration, and three showed a longer time of reaching arm deceleration, for reach to grasp movements to the large object than for those to the small object. CONCLUSION: Posteroventral pallidotomy seems to be beneficial in reducing bradykinesia of upper limb movements but may have "costs" to movement patterning, particularly for reach to grasp movements to objects of differing sizes. This study raises interesting questions about the role of the globus pallidus interna in coordinating stimulus bound visual information with appropriate motor patterning.

Left posteroventral pallidotomy results in a deficit in verbal memory.

Whilst pallidotomy is emerging as a popular approach to the treatment to Parkinson's disease, little is yet known about the cognitive effects of this procedure. This study presents 19 patients (6 right, 13 left) who were assessed both before and after the procedure on a battery of cognitive tests. The results indicate that subjects with left-sided lesions display significant decline in verbal memory between one and three months following the procedure. The results are consistent with the notion of either a classic amnesic syndrome or a deficit in striato-frontal working memory.

Cerebral glucose metabolism in Parkinson's disease with and without dementia.

Although cognitive impairment is commonly associated with Parkinson's disease, the relative importance of cortical and subcortical pathologic changes to the development of dementia is controversial. Characteristic abnormalities in cortical glucose metabolism have been reported previously in Alzheimer's disease, a disease in which cortical changes predominate. We measured cerebral glucose metabolism with positron emission tomography in 20 control subjects and in 14 patients with PD with mental status ranging from normal to severely demented to determine whether changes in cortical glucose metabolism occur in early PD and whether the degree and pattern of metabolic change relate to the severity of dementia. The patients were divided into demented and nondemented groups according to the results of neuropsychological assessment. Age-adjusted covariance analyses were performed, since the age distribution varied between groups. The nondemented patients with PD showed widespread cortical glucose hypometabolism without any selective temporoparietal defects. The pattern of glucose hypometabolism seen in the demented patients with PD resembled that described in patients with Alzheimer's disease; ie, there was a global decrease in glucose metabolism, with more severe abnormalities observed in the temporoparietal regions.

Diffuse Lewy body disease and progressive dementia in a young woman.

This report details the emergence of a progressive parkinsonian syndrome, dementia and behavioural disturbance in a 33 year-old woman which can be dated to the delivery of her first child. The findings of this case indicate that cortical Lewy body disease should be considered in any patient with temporoparietal dementia and idiopathic Parkinson's disease irrespective of the age of onset.

Cortical glucose metabolism in Parkinson's and Alzheimer's disease.

Characteristic regional patterns of decreased cerebral glucose metabolism (rCMRG) have been described in a variety of neurodegenerative conditions associated with dementia. The present study was undertaken to determine whether the metabolic pattern in Parkinson's disease is altered by the presence of impaired cognitive function. Glucose metabolism was measured with positron emission tomography in 6 patients with Parkinson's disease and dementia (PDD), 8 patients with Parkinson's disease and normal cognition (PD), and 6 patients with Alzheimer's disease (AD). All AD patients subsequently had the diagnosis proven neuropathologically at autopsy. Correlation coefficients of the metabolic rates across 32 regions of interest were calculated between each pair of patients. Q-component analysis of the correlation matrix showed that the AD and PD groups formed two distinct clusters and that the PDD group had a metabolic pattern which was similar to that of the AD group. Comparison of standardized rCMRG values showed that the PDD group differed from the PD group in having significantly lower relative rCMRG in the left perirolandic and bilateral angular gyrus regions. There were no significant differences between the PDD and AD groups. These results suggest a similar pattern of cortical dysfunction in both Alzheimer's disease and in Parkinson's disease/dementia.

Positron emission tomographic scanning demonstrates a presynaptic dopaminergic lesion in Lytico-Bodig. The amyotrophic lateral sclerosis-parkinsonism-dementia complex of Guam.

We performed positron emission tomography using 18F-6-fluorodopa on four Guamanians with an amyotrophic lateral sclerosis syndrome, eight Guamanians with parkinsonism, and seven clinically normal Guamanians; the results were compared with those of nine Vancouver control subjects. The Guamanian subjects had all been exposed to similar Chamorro lifestyles. The scans were analyzed using a graphic method that calculates a constant for whole striatal 18F-6-fluorodopa uptake. The parkinsonian subjects all had significantly reduced striatal 18F-6-fluorodopa uptake. The group with amyotrophic lateral sclerosis had significantly reduced uptake that was intermediate between that of the control group and the parkinsonian group. Two Guamanian normal subjects had reduced striatal 18F-6-fluorodopa uptake. The nigrostriatal dopaminergic lesion in Guamanian parkinsonism is similar to that found in idiopathic parkinsonism. The nigrostriatal lesions in the subjects with amyotrophic lateral sclerosis and the Guamanian normal subjects are examples of subclinical neuronal damage demonstrable in living subjects with positron emission tomography.

Parkinsonism with neuroacanthocytosis.

Two patients with neuroacanthocytosis are described. One presented with parkinsonism and the other resembled diurnal dystonia of the Segawa type. Both patients responded well to dopaminomimetic therapy. A PET scan with fluorodopa revealed a nigrostriatal deficit in the first patient.

Decreased efficacy of levodopa with carbidopa in parkinsonian patients after adrenal-to-caudate implants.

We studied 6 parkinsonian patients 6 weeks after unilateral adrenal-to-caudate implants. We withheld medications the night before each of 2 study days and gave the patients a single test dose of either a combination of levodopa and carbidopa, or levodopa alone in double-blind random order. We administered the modified Columbia scale, objective measurements of rigidity and movement velocity, and the pegboard test at regular intervals after the single test dose. The results revealed that the improvements in performance recorded by the Columbia scale and the pegboard test were significantly less on the side contralateral to the operation when patients received carbidopa, whereas there was no significant difference in performance between the 2 observations on the ipsilateral side. Carbidopa apparently crossed the disrupted blood-brain barrier and lowered the efficacy of levodopa.

Positron emission tomography in manganese intoxication.

We employed 6-fluorodopa to study the integrity of the nigrostriatal dopaminergic projection by positron emission tomography in 4 subjects with clinical features of mild parkinsonism caused by exposure to manganese. The 6-fluorodopa scans were normal. This finding suggests that in early manganism sufficient to cause parkinsonian deficits, damage may occur in pathways postsynaptic to the nigrostriatal system, probably involving striatal or pallidal neurons. Fluorodeoxyglucose scans showed decreased cortical glucose metabolism, the significance of which is discussed.

PET studies of parkinsonian patients treated with autologous adrenal implants.

Transplantation of autologous adrenal medulla tissue into the striatum has recently been proposed as a treatment for Parkinson's disease. We report the use of positron emission tomography (PET) to evaluate patients who had adrenal implants placed into the right caudate. 6-[18F] fluoro-L-dopa (6-FD) scans were performed to study the integrity and activity of the implant, and the nigrostriatal dopamine system before and six weeks after transplantation surgery. [68Ga] Gallium-ethylenediaminetetraacetate (Ga) scans were also performed to assess the blood brain barrier. The Ga scans performed on two patients showed increased permeability of the blood brain barrier at the surgical site. 6-FD PET scans in five patients did not show a consistent change in striatal uptake following adrenal medullary implantation after six weeks. Further assessment of implant viability with 6-FD PET scans after longer follow up may provide useful information if the blood-brain barrier becomes re-established with the passage of time.

A double-blind, placebo-controlled, dose-ranging study to investigate the safety and efficacy of CY 208-243 in patients with Parkinson's disease.

We carried out a double-blind rising dose study of a D-1 dopamine agonist, CY 208-243, in 6 parkinsonian patients. Deficits monitored by Columbia scores were significantly improved at single doses ranging from 5 to 40 mg, though efficacy was low. Used alone, CY 208-243 was not a satisfactory therapeutic agent, and toxicity data precluded further increases in dosage.

Aging of the nigrostriatal pathway in humans.

Progressive degeneration of functionally related groups of neurons occurs in certain infective, toxic, nutritional and genetically determined neurological diseases. It also takes place in normal aging, and several of the regions that undergo selective decay with the passage of time seem to be the same target regions that are afflicted in degenerative disorders such as Parkinson's disease. Alzheimer's disease and amyotrophic lateral sclerosis (ALS). Infective etiology is relatively easy to exclude by a combination of immunological tests and transfer experiments. Genetic causation can be rendered unlikely when large kindreds are available for study. Nutritional deprivation and acute or subacute toxicity are accessible to explanation by examining the environment. The most difficult mechanism of pathogenesis to refute is chronic toxic damage, where the lesion may derive from long-term exposure to a relatively widespread noxious agent or agents. Variations in involvement of individuals within a population may stem from differing capacities to activate or inactivate a toxin. Inherent in this concept of etiology is recognition that compensatory potential within the central nervous system may contribute to prolonged existence of subclinical lesions so that a latent period may exist for several decades, between causal event and the onset of symptoms. Furthermore, progressive clinical deterioration may take place even though the cause may have been transient, many years before.(ABSTRACT TRUNCATED AT 250 WORDS)

Cryoglobulinaemic neuropathy--a clinical spectrum.

In this report we present two cases who illustrate both ends of the spectrum of neuropathy with cryoglobulinaemia. Both patients responded well to treatment. A cryoglobulin assay should be done routinely in patients with mononeuritis multiplex of unknown cause, cutaneous vasculitis with cold sensitivity and chronic demyelinating neuropathies of unknown cause.