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Plasticity of primary motor cortex is severely impaired in Parkinson's disease and chronic dopaminergic treatment is reported not to rescue it. The effect of an acute dose of levodopa on cortical plasticity reported so far is variable. In this study, it was hypothesized that cortical plasticity would be restored in Parkinson's disease as a long duration response to treatment in stable responders while those with motor complications would have a reduction or loss of plasticity similar to the decay of long duration response of motor signs. Patients were carefully stratified based on their motor response to levodopa into stable responders (n=17), fluctuating non-dyskinetics (n=18) and fluctuating dyskinetics (n=20). Theta burst stimulation was applied to the motor cortex to induce long-term potentiation and long-term depression-like plasticity in both OFF and ON conditions. In OFF, stable responders could express both types of plasticity, fluctuating non-dyskinetics had long-term potentiation, but no long-term depression and both types of plasticity were lost in fluctuating dyskinetics. This suggests the presence of a long duration response in early stages of levodopa treatment and a gradual loss of chronic treatment benefit on plasticity, particularly for long-term depression, when motor complications develop. An acute dose of levodopa led to a worsening of long-term potentiation in fluctuating non-dyskinetic patients, and it did not have any effect on the plasticity that was absent in OFF in the fluctuating dyskinetic patients. Acute dosing led to a worsening of long-term depression in all the groups. In the fluctuating dyskinetic patients, there was a paradoxical potentiation instead of depression. Our results suggest that an acute non-physiological dopamine boost has a negative effect on cortical plasticity as disease advances. We propose that the loss of long duration response and the negative effect of acute doses on cortical plasticity with progression of disease may contribute to the pathophysiology of motor complications. Repeated non-physiological surges in synaptic dopamine during acute levodopa dosing could potentially lead to persistent dysfunction of key enzymes of the intracellular signalling cascade that are involved in the induction and maintenance of both forms of plasticity.

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Nondiagnostic biopsies were analyzed in a consecutive series of 407 patients undergoing computerized tomography (CT)-guided stereotactic biopsies. These were categorized as either negative biopsies, when normal tissue or nonspecific pathology was found, or inconclusive, when a definitive diagnosis could not be made although representative tissue was obtained. Nineteen biopsies (4.7%) were negative and 10 (2.4%) were inconclusive, giving an overall nondiagnostic biopsy rate of 7.1% (29 of the 407 cases). Suspected neoplastic masses (390 cases) were classified on the basis of their CT morphology into four groups: Group 1 included purely hypodense nonenhancing masses; Group 2 included isodense nonenhancing masses; Group 3 included ring-enhancing masses; and Group 4 included mixed-density enhancing masses. Although a higher proportion of hypodense nonenhancing masses (six of 56, or 10.7%) yielded a negative result, there was no statistically significant difference in the negative biopsy rates for the different CT categories (p = 0.06). The negative biopsy rates for the 6 years of the study, 1987 to 1992 (1987 being an incomplete year) were as follows: 13.3%, 6%, 3.2%, 3%, 5.8%, and 2.7%. There was no significant decrease in the negative biopsy rate as experience with this procedure increased (p = 0.20). A total of eight surgeons independently performed the biopsies. There was no significant difference (p = 0.24) in the negative biopsy rate of the surgeon with the most experience (124 biopsies, 2.4% negative biopsy rate) compared with that of the seven other surgeons combined (283 biopsies; 5.7% negative biopsy rate). These findings suggest that the yield in a stereotactic biopsy is independent of the CT appearance of the mass. Adherence to certain basic principles in patient and target selection will ensure a reasonable percentage of positive yield with stereotactic biopsy procedures even if the surgeon is relatively inexperienced. There does not appear to be a learning curve in the performance of CT-guided stereotactic biopsies. The management of patients with nondiagnostic biopsies is discussed.