Influence of white matter MRI hyper-intensities on acute l-dopa response in patients with Parkinson's disease.

OBJECTIVE: To determine whether brain white matter hyperintensities (WMH) influence l-dopa response in Parkinson's disease (PD) patients. METHODS: We prospectively evaluated 60 PD patients with an acute l-dopa challenge test, and assessed motor performance with the Movement Disorders Society revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) during "ON" and "OFF" medication states. Magnetic resonance images were examined using a visual semi-quantitative rating scale for quantification and distribution analysis of WMH. l-dopa challenge test response was correlated to extent and location of WMH, to determine a potential association between them. RESULTS: Subjects with greater deep WMH burden, showed less response to l-dopa on axial motor symptoms (R = -0.35; p < 0.027), when tested with Part III of the MDS-UPDRS before and after acute levodopa challenge. CONCLUSIONS: Results suggest WMH may affect response to l-dopa on axial function of PD patients, which could be due to either non-dopaminergic (cortico-basal ganglia) motor pathway disruption, or postsynaptic nigrostriatal pathway involvement.

Decision-making in Parkinson's disease patients with and without pathological gambling.

BACKGROUND AND PURPOSE: Pathological gambling (PG) in Parkinson's disease (PD) is a frequent impulse control disorder associated mainly with dopamine replacement therapy. As impairments in decision-making were described independently in PG and PD, the objective of this study was to assess decision-making processes in PD patients with and without PG. METHODS: Seven PD patients with PG and 13 age, sex, education and disease severity matched PD patients without gambling behavior were enrolled in the study. All patients were assessed with a comprehensive neuropsychiatric and cognitive evaluation, including tasks used to assess decision-making abilities under ambiguous or risky situations, like the Iowa Gambling Task (IGT), the Game of Dice Task and the Investment Task. RESULTS: Compared to PD patients without gambling behavior, those with PG obtained poorer scores in the IGT and in a rating scale of social behavior, but not in other decision-making and cognitive tasks. CONCLUSIONS: Low performance in decision-making under ambiguity and abnormal social behavior distinguished PD patients with PG from those without this disorder. Dopamine replacement therapy may induce dysfunction of the ventromedial prefrontal cortex and amygdala-ventral striatum system, thus increasing the risk for developing PG.

Prospective randomized 1-year follow-up comparison of bilateral subthalamotomy versus bilateral subthalamic stimulation and the combination of both in Parkinson's disease patients: a pilot study.

It has been suggested that potential risk of hemiballismus after subthalamotomy makes DBS preferable to ablation for IPD treatment; however, cost and the need for regular electrode control have also been observed as disadvantages to stimulation. The objective was to compare efficacy and safety of different surgical approaches to STN, in a prospective randomized pilot study. Sixteen consecutive IPD patients randomized to receive either: bilateral STN-DBS, bilateral subthalamotomy or unilateral subthalamotomy plus contralateral STN-DBS implantation, and followed for 12 months after surgery. One patient died and was excluded from the analysis. Total and motor UPDRS scores, as well as drug-induced dyskinesias improved significantly at 1 year follow-up, regardless of the procedure administered and without statistically significant differences between treatment modalities. Discrete changes were observed on ACE and MMSE scores. Psychiatric examination of patients subjected to bilateral stimulation and lesion, revealed slight increment in apathy and irritability scores, coinciding with significant deterioration of mentation, behaviour and mood as measured using the UPDRS. One patient presented persistent hemiballismus and required ulterior posteroventral pallidotomy. In this small group of patients, overall motor performance significantly improved after all three procedures, without major differences in outcome. Adverse events were, nevertheless, observed after both ablation and stimulation. The role of bilateral subthalamotomy in patients unable to receive a DBS electrode-implant merits further exploration in a larger series of patients with longer follow-up.

Functional surgery for Parkinson's disease treatment: a structured analysis of a decade of published literature.

The aim of this study was to analyse and compare published data during the last decade on the different approaches to Parkinson's disease surgery. Eighty-eight papers published between 1990 and 2001 fulfilled the inclusion criteria. Full-text and prospective papers on lesion and stimulation of GPi or STN were assessed. Descriptive analysis of surgery procedure and population under study was performed, as well as a meta-analysis of the most consistently reported variables. A total of 1702 patients underwent surgery with a mean age of 58.75 years (range 46.5 - 72.5), mean duration of illness 13.6 years (8.1 - 18.1) and a male:female ratio 1.5:1. Mean postoperative follow-up was 9 months (1 - 52). Single blind assessment was performed in two papers, while double blind evaluation was used in 6. In the GPi group, no difference was found between the pre- and postoperative levodopa equivalent daily dose (960.39 v. 943.13; p > 0.05), while the STN group showed a marked reduction (1104.8 v. 483.04; p < 0.05) of this dosage. Meta-analysis of the most consistently reported variables (UPDRS total score, UPDRS motor score, UPDRS ADL score and Schwab & England score showed that Nucleus, Bilaterality of Approach and Surgical Procedure were the best moderators for defining outcome. Bilateral DBS STN procedures proved to be associated with better outcome. Microelectrode recording was not found to be a moderator that influenced outcome. Although there was a significant improvement of dyskinesias among the different approaches described in the papers, the heterogeneity of data makes it impossible to perform a structured analysis on this item.

Mismatch between electrophysiologically defined and ventriculography based theoretical targets for posteroventral pallidotomy in Parkinson's disease.

OBJECTIVES: Over the past few years many reports have shown that posteroventral pallidotomy is an effective method for treating advanced cases of Parkinson's disease. The main differences with earlier descriptions were the use of standardised evaluation with new high resolution MRI studies and of single cell microrecording which can electrophysiologically define the sensorimotor portion of the internal globus pallidus (GPi). The present study was performed on a consecutive series of 40 patients with Parkinson's disease who underwent posteroventral pallidotomy to determine localisation discrepancies between the ventriculography based theoretical and the electrophysiologically defined target for posteroventral pallidotomy. METHODS: The tentative location of the posteroventral GPi portion was defined according to the proportional Talairach system. Single cell recording was performed in all patients. The definitive target was chosen according to the feasibility of recording single cells with GPi cell features, including the presence of motor drive and correct identification of the internal capsule and of the optic tract by activity recording and microstimulation. RESULTS: In all 40 patients the electrophysiologically defined sensorimotor portion of the GPi was lesioned, with significantly improved cardinal Parkinson's disease symptoms as well as levodopa induced dyskinesias, without damage to the internal capsule or optic tract. Significant differences between the localisation of the ventriculography based theoretical versus electrophysiological target were found in depth (p<0.0008) and posteriority (p<0.04). No significant differences were found in laterality between both approaches. Difference ranges were 8 mm for laterality, 6.5 mm for depth, and 10 mm for posteriority. CONCLUSIONS: Electrophysiologically defined lesion of GPi for posteroventral pallidotomy, shown to be effective for treating Parkinson's disease, is located at a significantly different site from the ventriculography based theoretical target.

Involuntary movements during thermolesion predict a better outcome after microelectrode guided posteroventral pallidotomy.

Eight of the first 15 patients with advanced Parkinson's disease who underwent microelectrode guided posteroventral pallidotomy developed transient abnormal involuntary movements during thermolesion, four of whom also did so during high frequency macrostimulation. Abnormal involuntary movements found before thermolesion were choreic, ballistic, or choreoathetoid in nature, usually persisted less than 60 minutes, and were contralateral to the site of thermolesion in six and bilateral in two of them. The appearance of abnormal involuntary movements during macrostimulation or thermolesion of the internal globus pallidus correlated with better surgical outcome as measured by UPDRS motor items and CAPIT timed test, so that they seem to be of prognostic value.