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P100 Deep brain stimulation and medication in Parkinson’s Disease: Changes in impulse control
Abstract / Basal Ganglia 1 (2011) 13–45
Results: In PD patients, we found a significantly altered integrity of premotor-basal ganglia fiber tracts at the level of putamen and ventrolateral thalamus in the connections from the dorsal premotor cortex (A). Furthermore, in PD group there were significant changes in the white matter underlying subthalamic nucleus and ventrolateral thalamus in the combined analysis of PMD and PMV connections (B). Conclusion: DTI and probabilistic tractography demonstrate altered morphological integrity of premotor-basal-ganglia pathways in PD patients. Moreover, it highlights the potential of this approach for investigating morphological pathologies of basal ganglia and cortical structures in PD. Future studies will need to address the clinical relevance of this morphological finding. In particular one will need to study the relationship between altered connectivity and the severity of frontal executive dysfunction and the potential use of tractography data as a biomarker for the evolution of PD. doi:10.1016/j.baga.2011.01.019
P100 Deep brain stimulation and medication in Parkinson’s Disease: Changes in impulse control D. Lulé, J. Heimrath, A.C. Ludolph, I. Uttner, J. Kassubek (Ulm) Effects of dopamine and dopamine agonist medication on impulsive behaviour and decision making in patients with Parkinson’s disease have been repeatedly reported. To reduce limitations of pharmacotherapy, deep brain stimulation (DBS) is increasingly used for the treatment of Parkinsonian motor symptoms, but the excellent efficacy of DBS contrasts with a growing number of reports that the treatment may result in behavioural complications. Fifteen patients with Parkinson’s disease with DBS were investigated with DBS electrical stimulation switched ON and OFF, respectively. Data were compared to those of 15 patients with Parkinson’s disease without DBS implantation under dopaminergic medication, matched for age and disease duration. Impulsive behaviour including gambling performance (IOWA gambling task) was measured together with neuropsychological tests regarding depression, current mood, and cognitive performance. Post-hoc analysis of CT scans demonstrated correct placement of electrodes in basal ganglia in 90% standard range. PD patients under high dopaminergic medication performed worse than DBS patients turned OFF in the gambling task. A significant interaction of performance and medication was observed. When DBS was turned ON, the differences in performance were less pronounced. In summary, the medication dose mainly explains differences in gambling performance: although DBS had a minor negative effect on impulsive behaviour, the positive effect of reduced DA dosis after DBS might reduce impulse control abnormalities. doi:10.1016/j.baga.2011.01.020
P101 Changes of the firing pattern of neurons in the subthalamic nucleus during reach-to-grasp movements in Parkinsonian patients M.H. Pötter-Nerger, R. Reese, F. Steigerwald, J.A. Haiden, J. Herzog, D. Falk, H.M. Mehdorn, G. Deuschl, L. Volkmann (Kiel, Würzburg) Objective: To characterise the firing pattern of movement-related subthalamic (STN) single cell activity during externally paced reach-to-grasp movements in Parkinsonian (PD) patients
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Methods: 12 PD patients (7 women, 5 men; mean ± SD age 62.0 ± 4.7 years) performed after overnight (>12 h) withdrawal of antiparkinsonian medication intraoperatively externally cued reach-to-grasp movements to a grip device while micorecording (band pass filtering 0.3–10 kHz, gain 100, sampling rate 25 kHz) with up to 5 stainless electrodes (BenGun). Single unit activity (SUA) was analysed in terms of firing pattern by calculating interspike interval histograms (ISIH, interval 0–0.25 s, bin 1 ms), which formed the basis for categorisation of neurons in bursting, irregular firing or tonic neurons. Furthermore autocorrelation functions (1000 ms, bin 1 ms, offset 500 ms) and consecutive power spectra (fast Fourier transformation, 1.953 Hz resolution, haming window) were calculated with respect to significant peaks between 1 and 100 Hz exceeding 5 times the standard deviations around the mean power. The oscillatory activity was classified according to the peak frequency of the power spectrum into d (1–3 Hz), h (4–7 Hz), a (8– 12 Hz), b (13–35 Hz) lower band c (36–60 Hz) or higher band c activity (60–100 Hz). Results: During the reach-to-grasp-movement 75/114 isolated STN neurons exhibited movement-associated activity changes. The mean SUA firing rate increased significantly (p = <0.01, T = 3.67) during movement (mean/SD 34.36 ± 32.73 Hz) compared to rest (mean/SD 31.98 ± 32.85 Hz), but the firing pattern (bursting, irregular or tonic) remained unchanged as revealed by ISIH. SUA oscillations were found in 28/114 neurons predominantly in the theta (15/28 neurons) and b band (8/28 neurons) at rest, but vanished with movement onset. Conclusion: Movement-related changes in the firing rate of STN neurons were accompanied by a decline of oscillations in the theta and b band of SUA. This finding underlines the hypothesis that b oscillations might antagonize motor-related processing within the basal ganglia and suppression of b-activity seems to facilitate voluntary movements. doi:10.1016/j.baga.2011.01.021
POSTER SESSION 1.2 Pharmocologic therapy P102 A long-term study on the safety of rivastigmine capsule and patch in mild to moderate Parkinson’s disease dementia A. Storch, P. Barone, P. De Deyn, M. Emre, J. Kulisevsky, W. Poewe, E. Pourcher, T. van Laar, N. Tenenbaum, S. Tekin (Dresden; Neapel, IT; Antwerpen, BE; Istanbul, TR; Barcelona, ES; Innsbruck, AT; Quebec, CA; Groningen, NL; East Hannover, NJ, US) Background: Rivastigmine is a pseudo irreversible cholinesterase inhibitor, previously shown to improve symptoms of dementia associated with Parkinson’s disease (PDD) in a 24-week placebo-controlled trial. The current study was set up to further investigate the safety of long-term treatment with rivastigmine capsule (12 mg/day) and patch (9.5 mg/24 h) in patients with mild to moderate PDD. New data will become available until March 2011 and will be added to the presentation. Methods: This is a 76-week, prospective, randomized, multicenter, open-label study. Patients have been 50–85 years old with mild to moderate PDD, a MMSE score of 10–26, and a Modified Hoehn and Yahr Stage (MHYS) <5 in ‘‘on’’-state. Patients receive either treatment with capsules titrated from 3 to 12 mg/day over 16 weeks, or with patches increasing the dose from 4.6 mg/24 h to 9.5 mg/24 h patch after 4 weeks. Primary outcome measures are the incidence rates of pre-defined adverse events (AEs; tremor, muscle rigidity,
Results: In PD patients, we found a significantly altered integrity of premotor-basal ganglia fiber tracts at the level of putamen and ventrolateral thalamus in the connections from the dorsal premotor cortex (A). Furthermore, in PD group there were significant changes in the white matter underlying subthalamic nucleus and ventrolateral thalamus in the combined analysis of PMD and PMV connections (B). Conclusion: DTI and probabilistic tractography demonstrate altered morphological integrity of premotor-basal-ganglia pathways in PD patients. Moreover, it highlights the potential of this approach for investigating morphological pathologies of basal ganglia and cortical structures in PD. Future studies will need to address the clinical relevance of this morphological finding. In particular one will need to study the relationship between altered connectivity and the severity of frontal executive dysfunction and the potential use of tractography data as a biomarker for the evolution of PD. doi:10.1016/j.baga.2011.01.019
P100 Deep brain stimulation and medication in Parkinson’s Disease: Changes in impulse control D. Lulé, J. Heimrath, A.C. Ludolph, I. Uttner, J. Kassubek (Ulm) Effects of dopamine and dopamine agonist medication on impulsive behaviour and decision making in patients with Parkinson’s disease have been repeatedly reported. To reduce limitations of pharmacotherapy, deep brain stimulation (DBS) is increasingly used for the treatment of Parkinsonian motor symptoms, but the excellent efficacy of DBS contrasts with a growing number of reports that the treatment may result in behavioural complications. Fifteen patients with Parkinson’s disease with DBS were investigated with DBS electrical stimulation switched ON and OFF, respectively. Data were compared to those of 15 patients with Parkinson’s disease without DBS implantation under dopaminergic medication, matched for age and disease duration. Impulsive behaviour including gambling performance (IOWA gambling task) was measured together with neuropsychological tests regarding depression, current mood, and cognitive performance. Post-hoc analysis of CT scans demonstrated correct placement of electrodes in basal ganglia in 90% standard range. PD patients under high dopaminergic medication performed worse than DBS patients turned OFF in the gambling task. A significant interaction of performance and medication was observed. When DBS was turned ON, the differences in performance were less pronounced. In summary, the medication dose mainly explains differences in gambling performance: although DBS had a minor negative effect on impulsive behaviour, the positive effect of reduced DA dosis after DBS might reduce impulse control abnormalities. doi:10.1016/j.baga.2011.01.020
P101 Changes of the firing pattern of neurons in the subthalamic nucleus during reach-to-grasp movements in Parkinsonian patients M.H. Pötter-Nerger, R. Reese, F. Steigerwald, J.A. Haiden, J. Herzog, D. Falk, H.M. Mehdorn, G. Deuschl, L. Volkmann (Kiel, Würzburg) Objective: To characterise the firing pattern of movement-related subthalamic (STN) single cell activity during externally paced reach-to-grasp movements in Parkinsonian (PD) patients
19
Methods: 12 PD patients (7 women, 5 men; mean ± SD age 62.0 ± 4.7 years) performed after overnight (>12 h) withdrawal of antiparkinsonian medication intraoperatively externally cued reach-to-grasp movements to a grip device while micorecording (band pass filtering 0.3–10 kHz, gain 100, sampling rate 25 kHz) with up to 5 stainless electrodes (BenGun). Single unit activity (SUA) was analysed in terms of firing pattern by calculating interspike interval histograms (ISIH, interval 0–0.25 s, bin 1 ms), which formed the basis for categorisation of neurons in bursting, irregular firing or tonic neurons. Furthermore autocorrelation functions (1000 ms, bin 1 ms, offset 500 ms) and consecutive power spectra (fast Fourier transformation, 1.953 Hz resolution, haming window) were calculated with respect to significant peaks between 1 and 100 Hz exceeding 5 times the standard deviations around the mean power. The oscillatory activity was classified according to the peak frequency of the power spectrum into d (1–3 Hz), h (4–7 Hz), a (8– 12 Hz), b (13–35 Hz) lower band c (36–60 Hz) or higher band c activity (60–100 Hz). Results: During the reach-to-grasp-movement 75/114 isolated STN neurons exhibited movement-associated activity changes. The mean SUA firing rate increased significantly (p = <0.01, T = 3.67) during movement (mean/SD 34.36 ± 32.73 Hz) compared to rest (mean/SD 31.98 ± 32.85 Hz), but the firing pattern (bursting, irregular or tonic) remained unchanged as revealed by ISIH. SUA oscillations were found in 28/114 neurons predominantly in the theta (15/28 neurons) and b band (8/28 neurons) at rest, but vanished with movement onset. Conclusion: Movement-related changes in the firing rate of STN neurons were accompanied by a decline of oscillations in the theta and b band of SUA. This finding underlines the hypothesis that b oscillations might antagonize motor-related processing within the basal ganglia and suppression of b-activity seems to facilitate voluntary movements. doi:10.1016/j.baga.2011.01.021
POSTER SESSION 1.2 Pharmocologic therapy P102 A long-term study on the safety of rivastigmine capsule and patch in mild to moderate Parkinson’s disease dementia A. Storch, P. Barone, P. De Deyn, M. Emre, J. Kulisevsky, W. Poewe, E. Pourcher, T. van Laar, N. Tenenbaum, S. Tekin (Dresden; Neapel, IT; Antwerpen, BE; Istanbul, TR; Barcelona, ES; Innsbruck, AT; Quebec, CA; Groningen, NL; East Hannover, NJ, US) Background: Rivastigmine is a pseudo irreversible cholinesterase inhibitor, previously shown to improve symptoms of dementia associated with Parkinson’s disease (PDD) in a 24-week placebo-controlled trial. The current study was set up to further investigate the safety of long-term treatment with rivastigmine capsule (12 mg/day) and patch (9.5 mg/24 h) in patients with mild to moderate PDD. New data will become available until March 2011 and will be added to the presentation. Methods: This is a 76-week, prospective, randomized, multicenter, open-label study. Patients have been 50–85 years old with mild to moderate PDD, a MMSE score of 10–26, and a Modified Hoehn and Yahr Stage (MHYS) <5 in ‘‘on’’-state. Patients receive either treatment with capsules titrated from 3 to 12 mg/day over 16 weeks, or with patches increasing the dose from 4.6 mg/24 h to 9.5 mg/24 h patch after 4 weeks. Primary outcome measures are the incidence rates of pre-defined adverse events (AEs; tremor, muscle rigidity,