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After more than 40 years of clinical use, levodopa (LD) remains the gold standard of symptomatic efficacy in the drug treatment of Parkinson's disease (PD). Compared with other available dopaminergic therapies, dopamine replacement with LD is associated with the greatest improvement in motor function. Long-term treatment with LD is, however, often complicated by the development of various types of motor response oscillations over the day, as well as drug-induced dyskinesias. Motor fluctuations can be improved by the addition of drugs such as entacapone or monoamine oxidase inhibitors, which extend the half-life of levodopa or dopamine, respectively. However, dyskinesia control still represents a major challenge. As a result, many neurologists have become cautious when prescribing therapy with LD. This review summarizes the available evidence regarding the use of LD to treat PD and will also address the issue of LD delivery as a critical factor for the drug's propensity to induce motor complications.

Background: Although movement disorders that occur following a stroke have long been recognised in short series of patients, their frequency and clinical and imaging features have not been reported in large series of patients with stroke., Methods: We reviewed consecutive patients with involuntary abnormal movements (IAMs) following a stroke who were included in the Eugenio Espejo Hospital Stroke Registry and they were followed up for at least one year after the onset of the IAM. We determined the clinical features, topographical correlations, and pathophysiological implications of the IAMs., Results: Of 1500 patients with stroke 56 developed movement disorders up to one year after the stroke. Patients with chorea were older and the patients with dystonia were younger than the patients with other IAMs. In patients with isolated vascular lesions without IAMs, surface lesions prevailed but patients with deep vascular lesions showed a higher probability of developing abnormal movements. One year after onset of the IAMs, 12 patients (21.4%) completely improved their abnormal movements, 38 patients (67.8%) partially improved, four did not improve (7.1%), and two patients with chorea died. In the nested case-control analysis, the patients with IAMs displayed a higher frequency of deep lesions (63% v 33%; OR 3.38, 95% CI 1.64 to 6.99, p<0.001). Patients with deep haemorrhagic lesions showed a higher probability of developing IAMs (OR 4.8, 95% CI 0.8 to 36.6)., Conclusions: Chorea is the commonest movement disorder following stroke and appears in older patients. Involuntary movements tend to persist despite the functional recovery of motor deficit. Deep vascular lesions are more frequent in patients with movement disorders.

Objective: To determine whether a positive L-dopa response in vascular parkinsonism (VP) is correlated with the presence of nigrostriatal pathology due to either vascular damage or neuronal cell loss., Methods: Seventeen patients with pathologically confirmed VP were selected from the pathological collection of the Queen Square Brain Bank for Neurological Disorders, and their L-dopa response during life was compared with the presence of macroscopic vascular damage in the nigrostriatal pathway and microscopic substantia nigra cell loss., Results: Ten of the twelve patients with a good or excellent response had macroscopic infarcts or lacunae caused by enlarged perivascular spaces in the basal ganglia or microscopic neuronal cell loss in the substantia nigra. In contrast, only one of the five patients with a moderate or no response had lacunae in the putamen, and none had lacunar infarcts or substantia nigra cell loss., Conclusion: These results suggest that a substantial number of patients with clinically suspected VP may respond with benefit to dopaminergic therapy, especially those with lesions in or close to the nigrostriatal pathway.

Purpose: To describe an MR imaging quantification method for estimation of total volumes of both white and gray matter subcortical lesions and ventricular cerebrospinal fluid (CSF) in the living human brain, and to determine the method's reliability., Methods: In 12 subjects, total subcortical lesion and ventricular CSF volumes were estimated using systematic sampling. Systematic sampling was performed on equidistant MR sections using a counting grid with systematically ordered intersection points. The grid was randomly positioned on each consecutive MR section. Each grid intersection point hitting the structure of interest represents a fixed known volume dependent on grid intersection point distance and the sum of the section thickness and section gap., Results: Total volume estimation of subcortical lesion and ventricular CSF takes 15 and 5 minutes per subject, respectively. Coefficients of error of the individual volume estimates ranged from .01 to .13 and are negligible to the coefficients of the group mean (range, .70 to .89). For subcortical lesion volume, the random intraobserver error yielded .04 and for ventricular CSF .02; the random interobserver error amounted to .11 and .04, respectively; and the systematic interobserver error was .15 and .04, respectively., Conclusion: The method described here for subcortical lesion and ventricular CSF volume estimation is accurate, reliable, valid, and fast.

Fifty four patients with idiopathic Parkinson's disease receiving levodopa therapy were studied. Thirty three of these patients displayed peak-dose dyskinesia. Neither the duration of Parkinson's disease nor the duration of levodopa therapy discriminated between patients with and patients without peak-dose dyskinesia. Consequently, these criteria could not determine whether the first appearance of peak-dose dyskinesia depends on the duration of Parkinson's disease--a factor that is related to the severity of the disease--or on the duration of levodopa therapy. A subgroup of nineteen patients with unilateral or unequivocally asymmetrical peak-dose dyskinesia was examined 12 hours after withdrawal of levodopa. A levodopa testdose provoked unilateral or unilateral preponderant peak-dose dyskinesia which always involved the most severely affected side and which also happened to be the side of onset of the disease. This demonstrates that the severity of Parkinson's disease is the main risk factor for peak-dose dyskinesia.