Amphetamines in the treatment of Parkinson's disease.
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Twenty-two patients with Parkinsonism were treated with levoamphetamine and 12 of these with dextroamphetamine. Levoamphetamine resulted in a significant improvement in disability from Parkinsonism, although the reduction in total disability, tremor, akinesia, and rigidity scores was slight (ca 20 percent). Dextroamphetamine in lower dosage also reduced disability by some 17 percent. The most disabled patients, including those also on levodopa, showed the greatest response to amphetamines. Previously, amphetamines have been reported to be a selective treatment for the oculogyric crises of post-encephalitic Parkinsonism. Amphetamines are thought to cause the release of catecholamines from central neurones. Their action in Parkinson's disease may be limited because of pre-existing striatal dopamine deficiency. Side-effects of amphetamines, anorexia, and CNS stimulation are different from those caused by levodopa in patients with Parkinson's disease. (+info)
Molecular modulation of inward and outward apical transporters of L-dopa in LLC-PK(1) cells.
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The present study examined the nature of the apical inward and outward L-3,4-dihydroxyphenylalanine (L-dopa) transporters in LLC-PK(1) cells and whether protein kinases differentially modulate the activities of these transporters. The apical inward transfer of L-dopa was promoted through an energy-dependent and sodium-insensitive transporter (Michaelis constant = 38 microM; maximum velocity = 2608 pmol. mg protein(-1). 6 min(-1)). This transporter was insensitive to N-(methylamino)-isobutyric acid but competitively inhibited by 2-aminobicyclo(2,2, 1)-heptane-2-carboxylic acid (BHC; IC(50) = 251 microM). Modulators of protein kinase A (cAMP, forskolin, IBMX, and cholera toxin), protein kinase G (cGMP, zaprinast, LY-83583 and sodium nitroprusside), and protein kinase C (phorbol 12,13-dibutirate and chelerythrine) failed to affect the accumulation of L-dopa. The Ca(2+)/calmodulin inhibitors calmidazolium and trifluoperazine inhibited L-dopa uptake (IC(50) of 72 and 55 microM, respectively). The inhibitory effect of calmidazolium on the accumulation of L-dopa was of the noncompetitive type. The organic anion inhibitor DIDS, but not p-aminohippurate, and the protein tyrosine kinase (PTK) inhibitor genistein significantly increased L-dopa accumulation, which was mainly due to inhibition of apical outward transfer of L-dopa. It is concluded that LLC-PK(1) cells take up L-dopa over the apical cell border through the L-type amino acid transporter, which appears to be under the control of Ca(2+)-calmodulin-mediated pathways. The apical outward transfer of L-dopa may be promoted through a DIDS-sensitive transport mechanism and appears to be under the tonic control of PTK. (+info)
Motor performance after posteroventral pallidotomy and VIM-thalamotomy in Parkinson's disease: a 1-year follow-up study.
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Twenty-three patients with Parkinson's disease underwent stereotactic surgery. To study the long-term motor performance, the patients were evaluated at the pre-operative period and at the 1st, 3rd, 6th, and 12th post-operative months, with the following scales: Unified Parkinson's Disease Rating Scale (UPDRS) motor score and Larsen's Scale for Dyskinesias. The patients under levodopa therapy were assessed both in "on" and "off" periods. Fourteen unilateral ventrolateral thalamotomies (VLT), 4 unilateral posteroventral pallidotomies (PVP), 2 bilateral PVP, and 3 VLT with contralateral PVP were performed. The motor improvement was significant and long-lasting in the "off" period, except for 2 patients. The "on" period quality improved, mainly due to the control of dyskinesias. The improvement of dyskinesias was long-lasting for the majority of the patients. There was no significant decrease in the levodopa dose. Three patients showed permanent complications, but none was severe. (+info)
P300 in newly diagnosed non-dementing Parkinson's disease: effect of dopaminergic drugs.
(60/1391)
Changes in cognitive function are an integral part of the clinical presentation of Parkinson's Disease (PD). P300 potential studies in early stages of Parkinson's disease are lacking and effect of L-dopa therapy on these potentials is controversial. In this study, changes in P300 potentials in early stages of PD and effects of dopaminergic therapy were investigated. P300 waves were elicited by standard auditory 'odd ball' paradigm and were recorded before the start of therapy and 15 days, 3 and 6 months after the start of L-dopa therapy in 25 newly diagnosed patients with idiopathic PD. All patients were classified according to Hoehn and Yahr scale. Minimental status examination (MMSE) was done in all. Control group had 20 normal subjects. The P300 latency was not significantly increased in early Parkinson's disease. This latency was reduced with dopaminergic therapy on 15th day, but increased later. Implications of the data are discussed. (+info)
Systematic review of acute levodopa and apomorphine challenge tests in the diagnosis of idiopathic Parkinson's disease.
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OBJECTIVES: To perform a systematic review of studies examining the diagnostic accuracy of acute challenge tests with levodopa and/or apomorphine in parkinsonian syndromes to assess their value in the diagnosis of idiopathic Parkinson's disease. METHODS: A literature search including Medline and the Cochrane Library was performed for studies published in any language comparing acute levodopa and/or apomorphine response with chronic levodopa therapy in parkinsonian syndromes. Abstracted sensitivity and specificity data were summarised using variance weighting and conditional logistic regression for studies comparing two challenge tests. RESULTS: Thirteen studies were located: four examining de novo patients and nine examining patients with well established idiopathic Parkinson's disease and non-parkinsonian conditions. Despite the significant heterogeneity in the methodologies employed, the comparable results suggest that this had little effect on the accuracy of the tests. The sensitivity for the diagnosis of established idiopathic Parkinson's disease was: apomorphine 0.86 (95% confidence interval (95% CI) 0.78-0.94), acute levodopa 0.75 (95% CI 0.64-0.85), and chronic levodopa therapy 0.91 (95% CI 0.85-0.99). The specificity for the diagnosis of established idiopathic Parkinson's disease was: apomorphine 0.85 (95% CI 0.74-0.96), acute levodopa 0.87 (95% CI 0. 77-0.97), and chronic levodopa therapy 0.77 (95% CI 0.61-0.93). The number of patients positive for each test divided by the number with clinically diagnosed de novo disease was: apomorphine 0.63 (95% CI 0. 56-0.70), acute levodopa 0.69 (95% CI 0.59-0.80), and chronic levodopa therapy 0.76 (95% CI 0.70-0.82). CONCLUSIONS: The accuracy of the acute levodopa and apomorphine challenge tests is similar to, but not superior than, that of chronic levodopa therapy in the diagnosis of idiopathic Parkinson's disease. As most patients will be given chronic dopamimetic therapy, these tests add nothing while causing significant adverse events and additional cost. (+info)
Development of an activity scale for individuals with advanced Parkinson disease: reliability and "on-off" variability.
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BACKGROUND AND PURPOSE: Functional mobility in people with advanced Parkinson disease, some of whom have a variable response to drug treatment, is often difficult to evaluate. The objectives of this study were to investigate the interrater reliability of measurements obtained with a scale designed to measure mobility and to determine the impact of self-rated dyskinesias and fluctuations on the measure. SSUBJECTS: Twenty-nine people with Parkinson disease and with disability and considerable disease duration (mean=11.7 years, SD=4.9, range=6-22) took part in the study. METHODS: The subjects' performance on a 10-item scale was videotaped. The videotapes were then scored by 2 independent raters, and the scores were used to determine interrater reliability. The stability of 6 repeated measurements was examined in the home situation, taking into account self-rated fluctuations of motor performance. RESULTS: Weighted Kappa values of agreement (.86-.98) confirmed the reliability between testers. Measurement during the "on" phase (when medication was working optimally) and the "off" phase (when the action of medication was strongly decreased or absent) led to different measurements. Measuring frequently within "on" and "off" phases gave relatively stable measurements for total function, bed transfers, and gait akinesia, the latter during the "off" phase only (intraclass correlation coefficients [ICCs]=.70-.93). However, more modest repeatability applied to transfers from a chair (ICC=.65-.67). CONCLUSION AND DISCUSSION: To ensure valid results in future effect studies, clinical differentiation between "on" and "off" phase measurements is proposed on the basis of patients' own perception of their medication status. (+info)
Dyskinesias and motor fluctuations in Parkinson's disease. A community-based study.
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We investigated the prevalence of dyskinesias and motor fluctuations, and the factors determining their occurrence, in a community-based population of patients with Parkinson's disease. Among 124 patients with Parkinson's disease, 87 (70%) had received a levodopa preparation. Among these 87 patients, 28% were experiencing treatment-induced dyskinesias and 40% response fluctuations. The prevalence of motor fluctuations was best predicted by disease duration and dose of levodopa, whereas dyskinesias could be best predicted by duration of treatment. Patients with a shorter time from symptom onset to initiation of levodopa and younger patients had developed motor complications earlier, and patients who had started treatment with a dopamine agonist had developed these treatment complications later. Although a satisfactory response to medication was associated with higher rates of motor complications, poor or moderate response was associated with lower quality of life in patients with a disease duration of /=10 years. We conclude that motor fluctuations are most strongly related to disease duration and dose of levodopa, and dyskinesias to duration of levodopa treatment. However, poorer quality of life associated with inadequate dosage of levodopa may be the price for a low rate of motor complications in patients with Parkinson's disease. (+info)
Centrally initiated postural adjustments in parkinsonian patients on and off levodopa.
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This study investigates the effects of parkinsonism and dopamine replacement therapy (levodopa) on centrally initiated postural activity preceding rising onto the toes. The electromyographic (EMG) and force magnitude, scaling, sequencing, and postural stabilization were compared when rising-to-toes under two conditions, slow/low versus fast/high, for parkinsonian patients and elderly control subjects. Parkinsonian subjects were tested after withholding their levodopa medication for 12-16 h and again 1 h after taking their medication when parkinsonian signs were diminished. Parkinsonian subjects showed reduced magnitudes and delayed timing of the postural and voluntary components of the rise-to-toes task, as if they had difficulty turning off the postural, tibialis anterior (TIB) component and initiating the voluntary, gastrocnemius (GAS) component. Dopamine improved the relative timing, as well as the magnitude of both postural and voluntary components of rise-to-toes. Although the magnitude of dorsiflexion torque was smaller for parkinsonian subjects ON and OFF than for healthy elderly controls, the parkinsonian subjects showed intact scaling of the magnitude of postural activity. Parkinsonian subjects do not perform the rise-to-toes task like normal subjects who are instructed to rise slowly; the relative timing of TIB and GAS activation was different even at comparable speeds of performance. Parkinsonian subjects, both ON and OFF, exhibited greater risk of falling than elderly control subjects when rising to toes. This increased risk of falling was reflected in a smaller safety margin between the peak center of mass (CoM) and peak center of pressure (CoP) during the task. The magnitude of mean postural dorsiflexion torque in the rise-to-toes task was highly correlated with a clinical rating scale of gait and balance, suggesting that force control is a critical factor influencing postural control in patients with Parkinson's disease. (+info)