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P 71 Levodopa modulates beta and gamma oscillations in the cortico-basal ganglia loop with a higher efficacy than the dopamine receptor agonist apomorphine in experimental Parkinsonism
Abstracts / Clinical Neurophysiology 128 (2017) e305–e412
gaze palsy is the eponymous feature in PSP and was significantly correlated with midbrain atrophy (p < 0.01, corrected), midbrain microstructural damage (p < 0.001, corrected), and regional functional connectivity loss in the midbrain (p < 0.001, corrected). Pronounced saccadized pursuit (p < 0.001) was a cardinal feature in MSA which was correlated with pontine atrophy and white matter damage in the middle cerebral peduncle (p < 0.001). Conclusions: Worse oculomotor performance in the diseasespecific domain was associated with more severely impaired regional macro- and microstructure and reduced regional functional connectivity in disease-specific brain structures. These findings increase our pathophysiological knowledge of the underlying parkinsonismassociated pathology and pave the way towards a videooculographic surrogate marker. References Gorges M, Müller H-P, Lulé, et al. Brain Imag Behav 2016;10:79–91. doi:10.1016/j.clinph.2017.06.146
Poster P 71 Levodopa modulates beta and gamma oscillations in the cortico-basal ganglia loop with a higher efficacy than the dopamine receptor agonist apomorphine in experimental Parkinsonism—J. Kühn, J. Haumesser, M. Beck, J. Altschüler, A. Kühn, V. Nikulin, C. van Riesen * (Charite Berlin, Neurologie, Berlin, Germany) ⇑
Corresponding author.
The pharmacotherapy of Parkinson’s disease (PD) is based on levodopa, and dopamine receptor agonists, such as apomorphine. Although both types of agents provide beneficial clinical effects on motor and non-motor symptoms in PD clinical efficiency and side effects differ substantially between levodopa and dopamine receptor agonists. Levodopa is known to provide a greater symptomatic relief than dopamine receptor agonists. Since long-term levodopa treatment often results in debilitating motor fluctuations, dopamine receptor agonists are recommended in younger patients. The pharmacodynamic basis of these profound differences is not understood so far. Levodopa and dopamine receptor agonists may have a different impact on beta and gamma oscillations in the cortico-basal ganglia loop that have been shown to be of importance for the pathophysiology of PD. We performed in vivo electrophysiological recordings in anesthetized dopamine-intact and dopaminedepleted rats compare the impact of levodopa or apomorphine on neuronal population oscillations. Our results demonstrated that levodopa had a higher potency than apomorphine to suppress the abnormal beta oscillations that are often associated with bradykinesia while simultaneously increasing the gamma oscillations often associated with increased movement. Our data suggests that the higher clinical efficacy of levodopa as well as some of its side effects, as e.g. dyskinesias may be based on its characteristic ability to modulate beta-/gamma-oscillation dynamics in the cortico-basal ganglia loop circuit. doi:10.1016/j.clinph.2017.06.147
e363
Poster P 72 Influence of anesthesia on the outcome in patients with Parkinson’s disease undergoing deep brain stimulation of the subthalamic nucleus—F. Blasberg 1,*, L. Wojtecki 1, J. Vesper 2, A. Schnitzler 1, S.J. Groiss 1 (1 Heinrich-Heine-Universität, Institut für klinische Neurowissenschaften und medizinische Psychologie, Düsseldorf, Germany, 2 Heinrich-Heine-Universität, Funktionelle Neurochirurgie und Stereotaxie, Düsseldorf, Germany) ⇑
Corresponding author.
Background: Currently, implantation of electrodes for Deep Brain Stimulation (DBS) as a treatment for patients with Parkinson’s Disease (PD) is usually performed under local anaesthesia (LA) to allow intraoperative testing of effects and side effects. Recently, several studies have indicated that surgery under general anaesthesia (GA) may lead to comparable outcomes. However, most of these studies did not compare the types of anesthesia directly. Objective: This study aims to investigate whether the type of anesthesia (LA vs. GA) affects the outcome of motor and cognitive symptoms and reduction of levodopa-equivalent daily dose (LEDD) after subthalamic nucleus (STN)-DBS over a period of one year in a large single center population. Methods: 48 patients underwent DBS in GA between 2008 and 2015 at the center of movement disorders in Düsseldorf. From the other 140 patients operated by the standard procedure in LA in the same period of time, 48 patients were matched to the GA group. These groups were compared regarding improvement in motor function measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) III, decrease of LEDD, setting of stimulation parameters, cognitive function measured with neuropsychological tests and occurrence of stimulation induced side effect. Results: Motor function measured by the UPDRS III score in the medication off, stimulation on state was significantly better in the LA group compared to the GA group. Subscore analysis revealed that axial symptoms ‘‘freezing” and ‘‘speech” were significantly worse in the GA group at three months and one year, respectively. Postoperative LEDD-reduction was significant in both groups and did not differ between the groups over the whole period of one year. There were no significant differences of stimulation amplitude and cognition between the groups. Stimulation induced side effects tended to be less frequent in the LA group but did not reach statistical significance. Conclusions: In our study, motor function of patients undergoing DBS surgery in LA improved significantly more over the period of one year postoperatively compared to those operated in GA. Furthermore postoperative stimulation induced side effects tended to be less frequent in the LA group. We therefore conclude that surgery in LA with intraoperative testing is still significantly advantageous for PD patients undergoing STN-DBS and should be first choice if there are no other specific limitations that make GA unavoidable. doi:10.1016/j.clinph.2017.06.148
Poster P 73 Shorter pulse width reduces gait ataxia associated with VIMDBS—D. Kroneberg 1,*, A.C. Meyer 1, G.H. Schneider 2, A. Kühn 1
gaze palsy is the eponymous feature in PSP and was significantly correlated with midbrain atrophy (p < 0.01, corrected), midbrain microstructural damage (p < 0.001, corrected), and regional functional connectivity loss in the midbrain (p < 0.001, corrected). Pronounced saccadized pursuit (p < 0.001) was a cardinal feature in MSA which was correlated with pontine atrophy and white matter damage in the middle cerebral peduncle (p < 0.001). Conclusions: Worse oculomotor performance in the diseasespecific domain was associated with more severely impaired regional macro- and microstructure and reduced regional functional connectivity in disease-specific brain structures. These findings increase our pathophysiological knowledge of the underlying parkinsonismassociated pathology and pave the way towards a videooculographic surrogate marker. References Gorges M, Müller H-P, Lulé, et al. Brain Imag Behav 2016;10:79–91. doi:10.1016/j.clinph.2017.06.146
Poster P 71 Levodopa modulates beta and gamma oscillations in the cortico-basal ganglia loop with a higher efficacy than the dopamine receptor agonist apomorphine in experimental Parkinsonism—J. Kühn, J. Haumesser, M. Beck, J. Altschüler, A. Kühn, V. Nikulin, C. van Riesen * (Charite Berlin, Neurologie, Berlin, Germany) ⇑
Corresponding author.
The pharmacotherapy of Parkinson’s disease (PD) is based on levodopa, and dopamine receptor agonists, such as apomorphine. Although both types of agents provide beneficial clinical effects on motor and non-motor symptoms in PD clinical efficiency and side effects differ substantially between levodopa and dopamine receptor agonists. Levodopa is known to provide a greater symptomatic relief than dopamine receptor agonists. Since long-term levodopa treatment often results in debilitating motor fluctuations, dopamine receptor agonists are recommended in younger patients. The pharmacodynamic basis of these profound differences is not understood so far. Levodopa and dopamine receptor agonists may have a different impact on beta and gamma oscillations in the cortico-basal ganglia loop that have been shown to be of importance for the pathophysiology of PD. We performed in vivo electrophysiological recordings in anesthetized dopamine-intact and dopaminedepleted rats compare the impact of levodopa or apomorphine on neuronal population oscillations. Our results demonstrated that levodopa had a higher potency than apomorphine to suppress the abnormal beta oscillations that are often associated with bradykinesia while simultaneously increasing the gamma oscillations often associated with increased movement. Our data suggests that the higher clinical efficacy of levodopa as well as some of its side effects, as e.g. dyskinesias may be based on its characteristic ability to modulate beta-/gamma-oscillation dynamics in the cortico-basal ganglia loop circuit. doi:10.1016/j.clinph.2017.06.147
e363
Poster P 72 Influence of anesthesia on the outcome in patients with Parkinson’s disease undergoing deep brain stimulation of the subthalamic nucleus—F. Blasberg 1,*, L. Wojtecki 1, J. Vesper 2, A. Schnitzler 1, S.J. Groiss 1 (1 Heinrich-Heine-Universität, Institut für klinische Neurowissenschaften und medizinische Psychologie, Düsseldorf, Germany, 2 Heinrich-Heine-Universität, Funktionelle Neurochirurgie und Stereotaxie, Düsseldorf, Germany) ⇑
Corresponding author.
Background: Currently, implantation of electrodes for Deep Brain Stimulation (DBS) as a treatment for patients with Parkinson’s Disease (PD) is usually performed under local anaesthesia (LA) to allow intraoperative testing of effects and side effects. Recently, several studies have indicated that surgery under general anaesthesia (GA) may lead to comparable outcomes. However, most of these studies did not compare the types of anesthesia directly. Objective: This study aims to investigate whether the type of anesthesia (LA vs. GA) affects the outcome of motor and cognitive symptoms and reduction of levodopa-equivalent daily dose (LEDD) after subthalamic nucleus (STN)-DBS over a period of one year in a large single center population. Methods: 48 patients underwent DBS in GA between 2008 and 2015 at the center of movement disorders in Düsseldorf. From the other 140 patients operated by the standard procedure in LA in the same period of time, 48 patients were matched to the GA group. These groups were compared regarding improvement in motor function measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) III, decrease of LEDD, setting of stimulation parameters, cognitive function measured with neuropsychological tests and occurrence of stimulation induced side effect. Results: Motor function measured by the UPDRS III score in the medication off, stimulation on state was significantly better in the LA group compared to the GA group. Subscore analysis revealed that axial symptoms ‘‘freezing” and ‘‘speech” were significantly worse in the GA group at three months and one year, respectively. Postoperative LEDD-reduction was significant in both groups and did not differ between the groups over the whole period of one year. There were no significant differences of stimulation amplitude and cognition between the groups. Stimulation induced side effects tended to be less frequent in the LA group but did not reach statistical significance. Conclusions: In our study, motor function of patients undergoing DBS surgery in LA improved significantly more over the period of one year postoperatively compared to those operated in GA. Furthermore postoperative stimulation induced side effects tended to be less frequent in the LA group. We therefore conclude that surgery in LA with intraoperative testing is still significantly advantageous for PD patients undergoing STN-DBS and should be first choice if there are no other specific limitations that make GA unavoidable. doi:10.1016/j.clinph.2017.06.148
Poster P 73 Shorter pulse width reduces gait ataxia associated with VIMDBS—D. Kroneberg 1,*, A.C. Meyer 1, G.H. Schneider 2, A. Kühn 1