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Background: Dopamine responsiveness (dopa-sensitivity) is an important parameter in the management of patients with Parkinson's disease (PD). For quantification of this parameter, patients undergo a challenge test with acute Levodopa administration after drug withdrawal, which may lead to patient discomfort and use of significant resources., Objective: Our objective was to develop a predictive model combining clinical scores and imaging., Methods: 350 patients, recruited by 13 specialist French centers and considered for deep brain stimulation, underwent an acute L-dopa challenge (dopa-sensitivity > 30%), full assessment, and MRI investigations, including T1w and R2* images. Data were randomly divided into a learning base from 10 centers and data from the remaining centers for testing. A machine selection approach was applied to choose the optimal variables and these were then used in regression modeling. Complexity of the modelling was incremental, while the first model considered only clinical variables, the subsequent included imaging features. The performances were evaluated by comparing the estimated values and actual valuesResults:Whatever the model, the variables age, sex, disease duration, and motor scores were selected as contributors. The first model used them and the coefficients of determination (R2) was 0.60 for the testing set and 0.69 in the learning set (p < 0.001). The models that added imaging features enhanced the performances: with T1w (R2 = 0.65 and 0.76, p < 0.001) and with R2* (R2 = 0.60 and 0.72, p < 0.001)., Conclusion: These results suggest that modeling is potentially a simple way to estimate dopa-sensitivity, but requires confirmation in a larger population, including patients with dopa-sensitivity < 30.

Besides antipsychotics, several drugs can induce parkinsonism. We review spontaneous notifications of drug-induced or -worsened parkinsonism to a French regional pharmacovigilance center between 1993 and 2009. During these 17 years, 20,855 adverse drug reactions have been reported, including 155 (0.7%) cases of drug-induced or -worsened parkinsonism. Most of the notifications have involved aged patients (48% between 60 and 79 years) and females (60%). "Seriousness" was found in 43.9% of cases. Worsening of parkinsonism occurred in 28 patients suffering from idiopathic Parkinson's disease. Sixty-nine percent of drug-induced or -worsened parkinsonism cases were observed during the first 3 months after introduction of the "suspect" drug (involving mainly central dopaminergic antagonists). A second peak (20%) was found 12 months after drug introduction (mainly caused by calcium channel blockers). The most frequently reported parkinsonian symptom was rigidity (78.7%). The three cardinal symptoms were found in 37.4% of notifications. Evolution was favorable (after partial or complete withdrawal of suspect drug[s]) in 88.7% of cases. Among the 261 suspect drugs, most involved central dopaminergic antagonists (49%), followed by antidepressants (8%), calcium channel blockers (5%), peripheral dopaminergic antagonists (5%), and H1 antihistamines (5%). Cases with lithium, valproic acid, amiodarone, anticholinesterases, or trimetazidine were also found. Three notifications were the result of pharmacokinetic interactions. We found that drug-induced or -worsened parkinsonism is an often "serious," but reversible, adverse drug reaction. It occurred more frequently between 60 and 79 years. Rigidity was the most frequently reported symptom. Approximately 50% of drug-induced or -worsened parkinsonism cases spontaneously reported were related to drugs other than antipsychotics. Drug-induced or -worsened parkinsonism can also be explained by pharmacokinetic drug interactions., (Copyright © 2011 Movement Disorder Society.)

Available evidence on the practice of acute pharmacological challenge tests in parkinsonian patients was reviewed by a committee of experts, which achieved a general consensus. The published data deal mainly with the acute administration of levodopa and apomorphine in Parkinson's disease. Such challenge may serve different purposes, e.g., research, diagnosis, or tailoring of treatment. Unique protocols describing the clinical setting and practice parameters are not available. The present paper describes the scientific background and supplies practical guidelines, whenever possible, to perform and evaluate acute challenge tests in parkinsonian syndromes. With the appropriate indication and setting, acute challenge tests are useful in diagnosis and therapy of Parkinson's disease and related disorders., (Copyright 2001 Movement Disorder Society.)

A historical study of the prescription of midodrine was carried out at the university hospital of Toulouse (France) between 1994 and 1998. The aim was to compare the observed prescriptions and the ideal prescriptions in accordance with the Summary of Product Characteristics (SPC). The analysis of 97 consecutive medical reports found discrepancies in prescription concerning the non-respect of contraindications and of potentially hazardous drug associations. Fifty-four (55.7 per cent) patients would have been excluded from prescription if the physicians had strictly respected the SPC. The inappropriate prescription of midodrine was associated with an increase in adverse drug reactions (ADRs). ADRs occurred in 34.0 per cent of cases overall and required drug discontinuation in 15.5 per cent.

1. The motor effect of the alpha 2 adrenoreceptor antagonist, idazoxan, was compared to that of L-dopa in MPTP-treated monkeys. 2. Idazoxan 2.0 mg/kg improved parkinsonian motor abnormalities which was comparable to the effects of a minimal effective dose of L-dopa. 3. At 2.0 and 5.0 mg/kg, the parkinsonian rigidity was the item most frequently alleviated by idazoxan (respectively 63.6% and 68.2%). 4. These findings provide support for the therapeutic utility of alpha 2 antagonists in the treatment of Parkinson's disease.

We have studied the frontal perfusion in the resting condition of two groups of patients with frozen gait: 10 patients with the syndrome of "isolated gait ignition failure" (IGIF) and 8 patients with idiopathic Parkinson's disease (PD) and severe "off" freezing. These patients were compared with two other groups: one including 20 age-matched volunteers as normal control subjects and the other one including 12 patients with progressive supranuclear palsy (PSP) as a positive control with expected frontal hypoperfusion. Frontal perfusion was assessed using single photon emission computed tomography (SPECT) regional cerebral blood flow measurement with intravenous 133Xenon. A significant frontal hypoperfusion was only present in the PSP group but not in the three others. These results do not support the hypothesis that start hesitations and freezing when walking are related to a frontal lobe dysfunction. However, it is possible that frontal neuronal dysfunction occurs without measurable cerebral blood flow changes in the resting condition.

We have studied the regional cerebral blood flow (rCBF) changes induced by the execution of a finger-to-thumb opposition motor task in the supplementary and primary motor cortex of two groups of parkinsonian patients on L-dopa medication, the first one without L-dopa induced dyskinesia (n = 23) and the other with moderate peak-dose dyskinesia (n = 15), and of a group of 14 normal subjects. Single photon emission tomography with i.v. 133Xe was used to measure the rCBF changes. The dyskinetic parkinsonian patients exhibited a pattern of response which was markedly different from those of the normal subjects and non-dyskinetic parkinsonian patients, with a significant overactivation in the supplementary motor area and the ipsi- and contralateral primary motor areas. These results are compatible with the hypothesis that an hyperkinetic abnormal involuntary movement, like L-dopa-induced peak dose dyskinesia, is due to a disinhibition of the primary and associated motor cortex secondary to an excessive outflow of the pallidothalamocortical motor loop.

We compared the rCBF changes induced by the execution of a finger-to-thumb opposition motor task in the cerebellar hemispheres of 12 normal subjects, 12 parkinsonian patients whose medication had been withheld for at least 18 h and 16 parkinsonian patients on medication using single photon emission tomography and i.v. 133Xe. The normal subjects and parkinsonian patients on medication exhibited the same pattern of response, with a significant increase in rCBF in the contralateral primary motor cortex and in the supplementary motor areas. No significant rCBF change was detected in the cerebellum of these two groups; this finding was expected since our technique cannot detect cerebellar activation when the motor task is executed at a relatively low rate and small amplitude as it was in this study. The parkinsonian patients off medication exhibited a markedly different pattern of activation characterized by a significant overactivation in the ipsilateral cerebellar hemisphere and a significant underactivation in the supplementary motor areas. These results suggest that parkinsonian patients off medication may try to compensate for their basal ganglia-cortical loop's dysfunction using other motor pathways involving cerebellar relays.

The approach to drug treatment of vertigo is almost exclusively symptomatic. There are 3 major goals for drug treatment of vertigo. The first one is to eliminate the hallucination of motion. Drugs with vestibular 'suppressant' properties are used for this purpose. The major vestibular suppressants are anticholinergic and antihistamine drugs. The second goal is to reduce the accompanying neurovegetative and psychoaffective signs (nausea, vomiting, anxiety). Antidopaminergics are used for this purpose. The third goal is to enhance the process of 'vestibular compensation' to allow the brain to find a new sensory equilibrium in spite of the vestibular lesion. Until now, the pharmacological manipulation of vestibular compensation has been assessed in animals but not in humans with vestibular lesions. Vestibular suppressant drugs delay rather than enhance compensation. A variety of other drugs is also used in the treatment of vertigo, including benzodiazepines, histaminergic agents, sympathomimetics and calcium antagonists. Their mechanism of action is poorly understood. The data base derived from clinical trials evaluating antivertigo medications is often questionable because of methodological limitations. This explains why habits of prescription are mainly empirical, and why striking differences can be noticed from one country to another. We can hope that new treatments may emerge from the present interest in receptor subclasses and neuromodulators of the vestibular system, and we must be ready to evaluate these potential new pharmacological agents with reliable clinical methods in humans.