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O Rascol

Publications and source records attributed to O Rascol.

At least 37 records · Page 2Linked to original sources
PubMed2001

Long-term mortality results of the randomized controlled study comparing bromocriptine to which levodopa was later added with levodopa alone in previously untreated patients with Parkinson's disease.

The present paper compares, in terms of mortality, two treatment regimens for Parkinson's disease (PD), i.e., bromocriptine later combined with levodopa versus levodopa only. Between 1982 and 1989, 60 PD patients (29 treated with levodopa alone [group D] and 31 receiving first bromocriptine followed by an association of bromocriptine + levodopa [group B/D]) were recruited. Data were updated in January 2000. Survival functions were estimated using Kaplan Meier product-limit method and comparison between the two groups with the log-rank test. Mortality was also compared with that of the general French population using standardized mortality ratios (SMRs). The mean duration of follow-up was 10.3 +/- 3.0 years. Seventeen patients died during the follow-up: nine in the group B/D and eight in the group D. The probability of survival at 10 years was 79.0% [95% confidence interval [CI]: 71.4-86.6] in group B/D and 72.9% [95% CI: 63.3-82.6] in group D. In comparison with the general French population, SMRs were not statistically different from 1, in the whole sample of PD patients (1.21, 95 % CI [0.71-1.95]), in group D (0.98 [0.42-1.93]), or in group B/D (1.53 [0.70-2.92]). In this population, we were unable to find any favourable effect of an early use of bromocriptine on mortality in PD in comparison with levodopa alone.

Aged↗
PubMed2001

Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease.

Dyskinesia is a frequent and disabling side effect in patients with Parkinson's disease treated with chronic dopa-therapy. Preclinical data in the 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) monkey suggest that alpha-2 antagonists may reduce dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. We assessed, in a pilot randomised placebo-controlled study, the effects of single oral doses (10 mg, 20 mg, and 40 mg) of idazoxan, an alpha-2 antagonist, on motor parkinsonian disability and L-DOPA-induced dyskinesia following an acute oral challenge of L-DOPA in 18 patients with Parkinson's disease. The severity of L-DOPA-induced dyskinesia improved after 20 mg idazoxan pretreatment, while there was no concommittant deterioration in the antiparkinsonian response to L-DOPA. These results suggest that blocking alpha-2 receptors in patients with Parkinson's disease might improve L-DOPA-induced dyskinesia without the cost of a return of parkinsonian symptomatology. Further studies are required to assess whether this property could have potential therapeutic applications in the long-term management of dyskinetic patients with Parkinson's disease.

Administration, Oral↗
PubMed2001

Amitriptyline treatment in chronic drug-induced headache: a double-blind comparative pilot study.

OBJECTIVE: To assess the effects of amitriptyline and sudden analgesic withdrawal on headache frequency and quality of life in patients suffering from chronic daily headache related to analgesics abuse. METHODS: Seventeen nondepressed patients with chronic drug-induced headache were included in a 9-week, parallel-group, randomized, double-blind, placebo-controlled study. After abrupt analgesic withdrawal, amitriptyline or an active placebo (trihexyphenidyl) was started. The primary efficacy variable was headache frequency recorded on a headache diary in the last 4 weeks of each treatment. The secondary efficacy variable was quality of life (Nottingham Health Profile). RESULTS: Headache frequency decreased by 45% in the amitriptyline group and by 28% in the trihexyphenidyl group. Amitriptyline enhanced all the dimensions of quality of life and significantly improved emotional reaction and social isolation. CONCLUSION: This pilot study suggests a beneficial effect of amitriptyline on headache frequency and quality of life for patients with chronic drug-induced headache.

Adult↗
PubMed2001

Within-session and between-session reproducibility of cerebral sensorimotor activation: a test--retest effect evidenced with functional magnetic resonance imaging.

The aim of the current study was to assess the reproducibility of functional magnetic resonance imaging (fMRI) brain activation signals in a sensorimotor task in healthy subjects. Because random or systematic changes are likely to happen when movements are repeated over time, the authors searched for time-dependent changes in the fMRI signal intensity and the extent of activation within and between sessions. Reproducibility was studied on a sensorimotor task called "the active task" that includes a motor output and a sensory feedback, and also on a sensory stimulation called "the passive task" that assessed the sensory input alone. The active task consisted of flexion and extension of the right hand. The subjects had performed it several times before fMRI scanning so that it was well learned. The passive task consisted of a calibrated passive flexion and extension of the right wrist. Tasks were 1 Hz-paced. The control state was rest. Subjects naïve to the MRI environment and non--MRI-naïve subjects were studied. Twelve MRI-naïve subjects underwent 3 fMRI sessions separated by 5 hours and 49 days, respectively. During MRI scanning, they performed the active task. Six MRI-naïve subjects underwent 2 fMRI sessions with the passive task 1 month apart. Three non--MRI-naïve subjects performed twice an active 2-Hz self-paced task. The data were analyzed with SPM96 software. For within-session comparison, for active or passive tasks, good reproducibility of fMRI signal activation was found within a session (intra-and interrun reproducibility) whether it was the first, second, or third session. Therefore, no within-session habituation was found with a passive or a well-learned active task. For between-session comparison, for MRI-naïve or non--MRI-naïve subjects, and with the active or the passive task, activation was increased in the contralateral premotor cortex and in ispsilateral anterior cerebellar cortex but was decreased in the primary sensorimotor cortex, parietal cortex, and posterior supplementary motor area at the second session. The lower cortical signal was characterized by reduced activated areas with no change in maximum peak intensity in most cases. Changes were partially reversed at the third session. Part of the test-retest effect may come from habituation of the MRI experiment context. Less attention and stress at the second and third sessions may be components of the inhibition of cortical activity. Because the changes became reversed, the authors suggest that, beyond the habituation process, a learning process occurred that had nothing to do with procedural learning, because the tasks were well learned or passive. A long-term memory representation of the sensorimotor task, not only with its characteristics (for example, amplitude, frequency) but also with its context (fMRI), can become integrated into the motor system along the sessions. Furthermore, the pattern observed in the fMRI signal changes might evoke a consolidation process.

Adult↗
PubMed2001

Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management.

Orthostatic hypotension is common in elderly patients, and is now considered to be an important prognostic factor for cognitive decline and mortality. In patients with Parkinson's disease, the prevalence of symptomatic orthostatic hypotension may be as high as 20%. Two factors could explain this high prevalence. First, dopaminergic drugs may induce or worsen orthostatic hypotension. Secondly, Parkinson's disease is a cause of primary autonomic failure with an involvement of the peripheral autonomic system as shown by the ubiquitous distribution of Lewy bodies and reduced iobenguane [metaiodobenzylguanidine (MIBG)] cardiac uptake. These pathological and pharmacological characteristics clearly differentiate autonomic failure of Parkinson's disease from multiple system atrophy. If autonomic abnormalities appear to be present from the first stage of the disease, early onset (within the first year) of symptomatic orthostatic hypotension in the course of parkinsonism can be considered as an exclusion criteria for idiopathic Parkinson's disease. No specific clinical trials have evaluated the effects of antihypotensive drugs in patients with Parkinson's disease and thus no specific therapeutic strategy can be recommended. The management of orthostatic hypotension in patients with Parkinson's disease should always start with patient education and nonpharmacological treatment. Drug therapy should be reserved for symptomatic patients who do not get benefit from nonpharmacological management. Among the available drugs, alpha1-adrenergic agonists (mainly midodrine) or plasma volume expanders (mainly fludrocortisone) are the most frequently used. There are also some drugs that are currently investigational such as yohimbine and droxidopa. Other drugs such as desmopressin or octreotide may be of interest in some situations. Domperidone is widely used in patients with parkinsonism with no proven effect on orthostatic hypotension.

Blood Volume↗
PubMed2000

A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa.

BACKGROUND: There is debate about whether the initial treatment for patients with Parkinson's disease should be levodopa or a dopamine agonist. METHODS: In this prospective, randomized, double-blind study, we compared the safety and efficacy of the dopamine D2-receptor agonist ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson's disease. If symptoms were not adequately controlled by the assigned study medication, patients could receive supplementary levodopa, administered in an open-label fashion. The primary outcome measure was the occurrence of dyskinesia. RESULTS: Eighty-five of the 179 patients in the ropinirole group (47 percent) and 45 of the 89 patients in the levodopa group (51 percent) completed all five years of the study. In the ropinirole group 29 of the 85 patients (34 percent) received no levodopa supplementation. The analysis of the time to dyskinesia showed a significant difference in favor of ropinirole (hazard ratio for remaining free of dyskinesia, 2.82; 95 percent confidence interval, 1.78 to 4.44; P<0.001). At five years, the cumulative incidence of dyskinesia (excluding the three patients who had dyskinesia at base line), regardless of levodopa supplementation, was 20 percent (36 of 177 patients) in the ropinirole group and 45 percent (40 of 88 patients) in the levodopa group. There was no significant difference between the two groups in the mean change in scores for activities of daily living among those who completed the study. Adverse events led to the early withdrawal from the study of 48 of 179 patients in the ropinirole group (27 percent) and 29 of 89 patients in the levodopa group (33 percent). The mean (+/-SD) daily doses given by the end of the study were 16.5+/-6.6 mg of ropinirole (plus 427+/-221 mg of levodopa in patients who received supplementation) and 753+/-398 mg of levodopa (including supplements). CONCLUSIONS: Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropinirole alone and supplementing it with levodopa if necessary.

Aged↗
PubMed2000

Mapping of spinocerebellar ataxia 13 to chromosome 19q13.3-q13.4 in a family with autosomal dominant cerebellar ataxia and mental retardation.

We examined a large French family with autosomal dominant cerebellar ataxia (ADCA) that was excluded from all previously identified spinocerebellar ataxia genes and loci. The patients-seven women and a 4-year-old boy-exhibited slowly progressive childhood-onset cerebellar gait ataxia associated with cerebellar dysarthria, moderate mental retardation (IQ 62-76), and mild developmental delays in motor acquisition. Nystagmus and pyramidal signs were also observed in some cases. This unique association of clinical features clearly distinguishes this new entity from other previously described ADCA. Cerebral magnetic-resonance imaging showed moderate cerebellar and pontine atrophy in two patients. We performed a genomewide search and found significant evidence for linkage to chromosome 19q13.3-q13.4, in an approximately 8-cM interval between markers D19S219 and D19S553.

Adult↗
PubMed2000

Sleep attacks and Parkinson's disease treatment.

Three patients with Parkinson's disease had so-called sleep attacks at the wheel while taking bromocryptine, lisuride pergolide, or piribedil. We believe that all dopamine agonists can induce sleep attacks.

Accidents, Traffic↗
PubMed2000

Lack of autonomic nervous dysfunction in progressive supranuclear palsy, a study of blood pressure variability.

Blood pressure and heart rate variability were analyzed in eight patients with progressive supranuclear palsy in comparison with two control groups (10 healthy patients and 10 patients with multiple system atrophy). Blood pressure and heart rate were recorded using digital photoplethysmography with the patient in supine position and during a head-up-tilt test (70 degrees for 10 minutes). Spectral analysis was performed using fast Fourier transformation for 512 consecutive systolic blood pressure and heart rate values. The head-up-tilt test induced a significant increase in systolic blood pressure in patients with progressive supranuclear palsy and in healthy patients and a significant systolic blood pressure decrease in patients with multiple system atrophy. During the head-up-tilt test, low-frequency energy of systolic blood pressure (70-130 mHz) that reflected baroreflex-dependent sympathetic tone also increased in patients with progressive supranuclear palsy and in healthy patients. By contrast, in patients with multiple system atrophy, the low-frequency energy of systolic blood pressure decreased significantly. The changes observed in the low-frequency band and the high-frequency band of heart rate (reflecting parasympathetic drive to the heart) were not different among the three groups. These data show the lack of impairment in autonomic nervous system activity in patients with progressive supranuclear palsy.

Aged↗
PubMed2000

The pharmacological therapeutic management of levodopa-induced dyskinesias in patients with Parkinson's disease.

The clinical management of levodopa-induced dyskinesia is difficult. Once present, dyskinesias are only partially improved by lowering the daily dose of levodopa and co-administering a D2 dopamine agonist. Therefore it appears to be necessary to use an NMDA-antagonist, such as amantadine, as an antidyskinetic agent. Clozapine may also improve dyskinesia without worsening akinesia, but it requires strict haematological monitoring. A long-term continuous subcutaneous infusion of apomorphine significantly reduces the dose of levodopa required, thereby markedly reducing dyskinesia, but this is difficult from a practical point of view. If none of these pharmacological strategies is successful, surgery should then be considered. Since the management of established levodopa-induced dyskinesia is difficult and often disappointing, efforts should be encouraged to try to prevent the occurrence of dyskinesia, before levodopa priming. This seems to be best achieved by the use of D2 dopamine agonists in the early stages of the disease, before, or in combination with, levodopa.

Animals↗
PubMed2000

Lorazepam-induced modifications of saccadic and smooth-pursuit eye movements in humans: attentional and motor factors.

In a placebo-controlled, double-blind study, we measured the effects of low dose lorazepam on attentional and motor factors involved in saccadic and smooth pursuit eye movements. We manipulated the temporal interval between the extinction of the central fixation target and the appearance of a second eccentric target (gap/overlap step paradigm). The second target was either stationary (saccade trial) or moving in a direction opposite to the step (pursuit trial). Gap/overlap effects on the latency of saccadic and smooth pursuit eye movements were measured before and after oral intake of either lorazepam or placebo. Pharmacological effects on the dynamics and the accuracy of both types of eye movements were also investigated. In 14 healthy volunteers, we found that the temporal interval between fixation target offset and eccentric target onset modulates the latency of saccadic and smooth pursuit eye movements in a similar way. As compared to placebo, lorazepam significantly increased the latency of both types of eye movements, but did not modify the gap/overlap effect. Moreover, lorazepam significantly decreased the peak velocity of the first saccade towards the eccentric stationary target, as well as the gain of tracking towards the eccentric moving target. However, the overall accuracy of both behaviors was not significantly affected, indicating that systematic errors in foveating or tracking were detected and corrected by appropriate corrective or catch-up saccades, respectively. Results are discussed in terms of shared/different mechanisms for saccadic and pursuit systems in primates.

Adult↗