(1/6239) Dopamine correlates of neurological and psychological status in untreated Parkinsonism.
Thirty-seven untreated Parkinsonism patients showed significant positive correlations among decreased excretion of free dopamine, MMPI scores indicative of schizophrenic-like looseness of thinking, and the severity of all Parkinsonism signs except tremor. The data could indicate that abnormalities of dopamine metabolism may underlie both the motor and mental abnormalities of Parkinsonism. (+info)
(2/6239) 2,3 diphosphoglycerate in Parkinson's disease.
The red cell 2,3 DPG, the most important factor for oxygen delivery in the tissues, was found to be increased in Parkinsonism patients compared with controls. The aging process seems not to be a factor in the increased 2,3 DPG concentration. Other factors relevant to raised 2,3 DPG level such as physical activity, increased oxygen requirements, and metabolic changes are discussed. (+info)
(3/6239) Visual control of locomotion in Parkinson's disease.
The effect of placing parallel lines on the walking surface on parkinsonian gait was evaluated. To identify the kind of visual cues (static or dynamic) required for the control of locomotion, we tested two visual conditions: normal lighting and stroboscopic illumination (three flashes/s), the latter acting to suppress dynamic visual cues completely. Sixteen subjects with idiopathic Parkinson's disease (nine males, seven females; mean age 68.8 years) and the same number of age-matched controls (seven males; nine females, mean age 67.5 years) were studied. During the baseline phase, Parkinson's disease patients walked with a short-stepped, slow velocity pattern. The double limb support duration was increased and the step cadence was reduced relative to normal. Under normal lighting, visual cues from the lines on the walking surface induced a significant improvement in gait velocity and stride length in Parkinson's disease patients. With stroboscopic illumination and without lines, both groups reduced their stride length and velocity but the changes were significant only in the Parkinson's disease group, indicating greater dependence on dynamic visual information. When stroboscopic light was used with stripes on the floor, the improvement in gait due to the stripes was suppressed in parkinsonian patients. These results demonstrate that the perceived motion of stripes, induced by the patient's walking, is essential to improve the gait parameters and thus favour the hypothesis of a specific visual-motor pathway which is particularly responsive to rapidly moving targets. Previous studies have proposed a cerebellar circuit, allowing the visual stimuli to by-pass the damaged basal ganglia. (+info)
(4/6239) Object location learning and non-spatial working memory of patients with Parkinson's disease may be preserved in "real life" situations.
The presence of a spatial memory deficit in Parkinson's disease (PD) is still a matter of discussion. Nineteen PD patients and 16 controls were given two spatial tests and a non-spatial task. First, the subject was led into a room containing 4 objects and had 10 s to memorize their location. After being led outside, the subject had to place icons representing the objects on a map of the room. Differences between the real and estimated locations were evaluated. Afterwards, the subject had to choose a map showing the correct arrangement of objects from 4 alternatives. Locations of some objects were changed before the second test. The subject had 10 s to detect these changes. One point was given for each change or its absence detected. In the non-spatial working memory task, 8 cards of different shapes were used. The subject had to select a different card each time while the cards were shuffled between choices. Errors consisted of selecting previously chosen cards. The means of the above measures for both groups were compared. Absence of any significant differences suggests that PD patients perform well in "real life" memory tests in contrast to similar computerized tests. (+info)
(5/6239) Impairment in preattentive visual processing in patients with Parkinson's disease.
We explored the possibility of whether preattentive visual processing is impaired in Parkinson's disease. With this aim, visual discrimination thresholds for orientation texture stimuli were determined in two separate measurement sessions in 16 patients with idiopathic Parkinson's disease. The results were compared with those of 16 control subjects age-matched and 16 young healthy volunteers. Discrimination thresholds were measured in a four-alternative spatial forced-choice paradigm, in which subjects judged the location of a target embedded in a background of distractors. Four different stimulus configurations were employed: (i) a group of vertical targets among horizontal distractors ('vertical line targets'); (ii) targets with varying levels of orientation difference on a background of spatially filtered vertically oriented noise ('Gaussian filtered noise'); (iii) one 'L' among 43 '+' signs ('texton'), all of which assess preattentive visual processing; and (iv) control condition, of one 'L' among 43 'T' distractors ('non-texton' search target), which reflects attentive visual processing. In two of the preattentive tasks (filtered noise and texton), patients with Parkinson's disease required significantly greater orientation differences and longer stimulus durations, respectively. In contrast, their performance in the vertical line target and non-texton search target was comparable to that of the matched control subjects. These differences were more pronounced in the first compared with the second session. Duration of illness and age within the patient group correlated significantly with test performance. In all conditions tested, the young control subjects performed significantly better than the more elderly control group, further indicating an effect of age on this form of visual processing. The results suggest that, in addition to the well documented impairment in retinal processing, idiopathic Parkinson's disease is associated with a deficit in preattentive cortical visual processing. (+info)
(6/6239) The effects of posteroventral pallidotomy on the preparation and execution of voluntary hand and arm movements in Parkinson's disease.
We studied the effect of posteroventral pallidotomy on movement preparation and execution in 27 parkinsonian patients using various motor tasks. Patients were evaluated after overnight withdrawal of medication before and 3 months after unilateral pallidotomy. Surgery had no effect on initiation time in unwarned simple and choice reaction time tasks, whereas movement time measured during the same tasks was improved for the contralesional hand. Movement times also improved for isometric and isotonic ballistic movements. In contrast, repetitive, distal and fine movements measured in finger-tapping and pegboard tasks were not improved after pallidotomy. Preparatory processes were investigated using both behavioural and electrophysiological measures. A precued choice reaction time task suggested an enhancement of motor preparation for the contralesional hand. Similarly, movement-related cortical potentials showed an increase in the slope of the late component (NS2) when the patients performed joystick movements with the contralesional hand. However, no significant change was found for the early component (NS1) or when the patient moved the ipsilesional hand. The amplitude of the long-latency stretch reflex of the contralesional hand decreased after surgery. In summary, the data suggest that pallidotomy improved mainly the later stages of movement preparation and the execution of proximal movements with the contralesional limb. These results provide detailed quantitative data on the impact of posteroventral pallidotomy on previously described measures of upper limb akinesia in Parkinson's disease. (+info)
(7/6239) Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson's disease. The Parkinson Study Group.
BACKGROUND: Drug-induced psychosis is a difficult problem to manage in patients with Parkinson's disease. Multiple open-label studies have reported that treatment with clozapine at low doses ameliorates psychosis without worsening parkinsonism. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of low doses of clozapine (6.25 to 50 mg per day) in 60 patients at six sites over a period of 14 months. The patients (mean age, 72 years) had idiopathic Parkinson's disease and drug-induced psychosis of at least four weeks' duration. All the patients continued to receive fixed doses of antiparkinsonian drugs during the four weeks of the trial. Blood counts were monitored weekly in all the patients. RESULTS: The mean dose of clozapine was 24.7 mg per day. The patients in the clozapine group had significantly more improvement than those in the placebo group in all three of the measures used to determine the severity of psychosis. The mean (+/-SE) scores on the Clinical Global Impression Scale improved by 1.6+/-0.3 points for the patients receiving clozapine, as compared with 0.5+/-0.2 point for those receiving placebo (P<0.001). The score on the Brief Psychiatric Rating Scale improved by 9.3+/-1.5 points for the patients receiving clozapine, as compared with 2.6+/-1.3 points for those receiving placebo (P=0.002). The score on the Scale for the Assessment of Positive Symptoms improved by 11.8+/-2.0 points for the patients receiving clozapine, as compared with 3.8+/-1.9 points for those receiving placebo (P=0.01). Seven patients treated with clozapine had an improvement of at least three on the seven-point Clinical Global Impression Scale, as compared with only one patient given placebo. Clozapine treatment improved tremor and had no deleterious effect on the severity of parkinsonism. In one patient, clozapine was discontinued because of leukopenia. CONCLUSIONS: Clozapine, at daily doses of 50 mg or less, is safe and significantly improves drug-induced psychosis without worsening parkinsonism. (+info)
(8/6239) A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.
Autosomal recessive juvenile parkinsonism (AR-JP, PARK2; OMIM 602544), one of the monogenic forms of Parkinson's disease (PD), was initially described in Japan. It is characterized by early onset (before age 40), marked response to levodopa treatment and levodopa-induced dyskinesias. The gene responsible for AR-JP was recently identified and designated parkin. We have analysed the 12 coding exons of the parkin gene in 35 mostly European families with early onset autosomal recessive parkinsonism. In one family, a homozygous deletion of exon 4 could be demonstrated. By direct sequencing of the exons in the index patients of the remaining 34 families, eight previously undescribed point mutations (homozygous or heterozygous) were detected in eight families that included 20 patients. The mutations segregated with the disease in the families and were not detected on 110-166 control chromosomes. Four mutations caused truncation of the parkin protein. Three were frameshifts (202-203delAG, 255delA and 321-322insGT) and one a nonsense mutation (Trp453Stop). The other four were missense mutations (Lys161Asn, Arg256Cys, Arg275Trp and Thr415Asn) that probably affect amino acids that are important for the function of the parkin protein, since they result in the same phenotype as truncating mutations or homozygous exon deletions. Mean age at onset was 38 +/- 12 years, but onset up to age 58 was observed. Mutations in the parkin gene are therefore not invariably associated with early onset parkinsonism. In many patients, the phenotype is indistinguishable from that of idiopathic PD. This study has shown that a wide variety of different mutations in the parkin gene are a common cause of autosomal recessive parkinsonism in Europe and that different types of point mutations seem to be more frequently responsible for the disease phenotype than are deletions. (+info)