Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial

Lhommée, Eugénie; Wojtecki, Lars; Czernecki, Virginie; Witt, Karsten; Maier, Franziska; Tonder, Lisa; Timmermann, Lars; Hälbig, Thomas D.; Pineau, Fanny; Durif, Franck; Witjas, Tatiana; Pinsker, Marcus O.; Mehdorn, Maximilian; Sixel‐Döring, Friederike; Kupsch, Andreas; Krüger, Rejko; Elben, Saskia; Chabardès, Stéphan; Thobois, Stéphane; Brefel‐Courbon, Christine; Ory‐Magne, Fabienne; Régis, J.; Maltête, David; Sauvaget, Anne; Rau, Jörn; Schnitzler, Alfons; Schüpbach, Michaël; Schade‐Brittinger, Carmen; Deuschl, Günther; Houeto, Jean‐Luc; Krack, Paul; Négovanska, Vélina; Welter, Marie‐Laure; Corvol, Jean‐Christophe; Agid, Yves; Navarro, Soledad; Meier, Niklaus; Hartmann, Andréas; Hesekamp, Helke; Cornu, Philippe; Möller, Bettina; Nebel, Adelheid; Raethjen, Jan; Knudsen, Karina; Volkmann, Jens; Falk, Daniela; Paschen, Steffen; Meister, Ingo G.; Kuhn, Jens; Donner, Kerstin; Kessler, Josef; Barbe, Michael T.; Fink, Gereon R.; Maarouf, Mohammad; Kühn, Andrea A.; Müller, Bianca; Faust, Katharina; Gruber, Doreen; Schneider, Gerd‐Helge; Seigneuret, Éric; Pollak, Pierre; Fraix, Valérie; Kistner, Andrea; Rascol, Olivier; Arbus, Christophe; Danet, Lola; Chaynes, Patrick; Groiss, Stefan Jun; Hartmann, Christian; Südmeyer, Martin; Partowinia-Peters, Mahnaz; Vesper, Jan; Severine, Ledily
,; Damier, Philippe; Raoul, Sylvie; Trenkwalder, Claudia; Richter-Dreske, Wenke; Wächter, Tobias; Weiß, Daniel; Alexandro, Eusebio
,; Azulay, J.-P.; Polo, Gustavo; Pinto, Serge; Levin, Johannes; Dornier, Stephanie; Pene, Fredy; Hourton, Delphine; Quintin, Mathieu; Hoffart-Jourdain, Cecile; Helene, Brocvielle
,; Balthasar, Kerstin; Stein, Meryem; Harnisch, Susanne; Reuß, Alexander; Aminossadati, Behnaz; Nasemann, Christian; Oertel, Wolfgang H.; Bataille, B.; Hellwig, Dieter; Gharabaghi, Alireza; Amtage, Florian; Mertens, Patrick; Kloß, Manja; Post, Bart; Speelman, Hans

doi:10.1016/s1474-4422(18)30035-8

Cited by 119 publications

(121 citation statements)

References 30 publications

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“…Accordingly, reasonable maintenance dose of Parkinson's disease treatments after surgery might prevent the occurrence of neuropsychiatric symptoms, including emotional processing disturbances (Dujardin, Blairy, Defebvre, Krystkowiak, et al, 2004b;Thobois et al, 2010). Our results would be compatible with the postoperative improvements in neuropsychiatric complications recently demonstrated in a randomized controlled trial of STN DBS versus levodopa (Lhommee et al, 2018).…”

Section: Clinical Considerationssupporting

confidence: 86%

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Different effects of levodopa and subthalamic stimulation on emotional conflict in Parkinson's disease

Martínez‐Fernández

Kibleur

Chabardès

et al. 2018

Human Brain Mapping

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Parkinson's disease impairs the decoding of emotional stimuli reflecting alterations of the limbic cortico‐subcortical network. The objective of this study was to assess and compare the behavioral and electrophysiological effects of both levodopa and subthalamic stimulation on emotional processing in Parkinson's disease. Operated patients (n =16) and matched healthy subjects performed an emotional Stroop task, in which the emotion expressed by a face must be recognized while ignoring an emotional distractive word and that includes a neutral control sub‐task. Patients were tested in the four possible treatment conditions (off stim/off med; on stim/off med; off stim/on med; and on stim/on med). High‐resolution electroencephalography was recorded while performing the task. Patients made significantly more mistakes in facial emotion recognition than healthy subjects (p < .005). Untreated patients performed worse in the emotional trials than in the control sub‐task (p < .05). Fearful faces induced significantly slower reaction times than happy faces in patients (p = .0002), but not in the healthy subjects. The emotional Stroop effect with levodopa was significantly higher than with subthalamic stimulation when fearful faces were assessed (p = .0243). Conversely, treatments did not modulate the Stroop effect of the control sub‐task. EEG demonstrated that, compared with the untreated state, levodopa but not subthalamic stimulation significantly increases the amplitude of the event‐related potential N170 (p = .002 vs. p = .1, respectively), an electrophysiological biomarker of early aspects of facial processing. The activity of the N170 cortical sources within the right fusiform gyrus was increased by levodopa (p < .05) but not by stimulation. While levodopa normalizes the recognition of emotional facial expression and early EEG markers of emotional processing, subthalamic stimulation does not. Thus, operated patients require dopaminergic medication in addition to stimulation to treat emotional symptoms of Parkinson's disease.

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Section: Clinical Considerationssupporting

confidence: 86%

“…In contrast to apathy, dopaminergic stimulation in the Parkinson's disease damaged mesocorticolimbic system might increase alertness and enhance sensitivity toward emotions (Kulisevsky, Pagonabarraga, & Martinez-Corral, 2009 (Lhommee et al, 2018).…”

Section: Clinical Considerationsmentioning

confidence: 99%

Different effects of levodopa and subthalamic stimulation on emotional conflict in Parkinson's disease

Martínez‐Fernández

Kibleur

Chabardès

et al. 2018

Human Brain Mapping

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“…The levodopa dose was reduced by 39% in the DBS group while it was increased by 21% in the group with best medical treatment. Hypo‐ and hyperdopaminergic behavioral symptoms (like apathy or mania) were significantly reduced in the neurostimulation vs. the medical treatment group (Lhommée et al , ).…”

Section: Clinical Effects Of Dbsmentioning

confidence: 99%

Cellular, molecular, and clinical mechanisms of action of deep brain stimulation—a systematic review on established indications and outlook on future developments

et al. 2019

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Deep brain stimulation ( DBS ) has been successfully used to treat movement disorders, such as Parkinson's disease, for more than 25 years and heralded the advent of electrical neuromodulation to treat diseases with dysregulated neuronal circuits. DBS is now superseding ablative techniques, such as stereotactic radiofrequency lesions. While serendipity has played a role in developing DBS as a therapy, research during the past two decades has shown that electrical neuromodulation is far more than a functional lesion that can be switched on and off. This understanding broadens the field to enable new types of stimulation, clinical indications, and research. This review highlights the complex effects of DBS from the single cell to the neuronal network. Specifically, we examine the electrical, cellular, molecular, and neurochemical mechanisms of DBS as applied to Parkinson's disease and other emerging applications.

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“…The DBS group showed reduced dopaminergic medication use, especially dopamine agonist, because the levodopa‐equivalent dose was reduced by 39%. In contrast, dopaminergic medication doses increased by 21% in the medical therapy alone group . Although the optimal timing of DBS still needs to be defined, it is advisable to have a tailored DBS treatment criterion for patients with PD older than 70 years old, and in patients with disease duration of <7 years.…”

Section: Invasive Brain Stimulation In Pd Dbsmentioning

confidence: 99%

Invasive and Noninvasive Brain Stimulation in Parkinson's Disease: Clinical Effects and Future Perspectives

Chen

2019

Clin Pharma and Therapeutics

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In this review, we discuss the clinical and electrophysiological effects and the future directions of invasive and noninvasive brain stimulations in Parkinson's disease (PD). Deep brain stimulation (DBS) can improve motor symptoms in moderate to advanced PD. However, the optimal stimulation paradigm for nonmotor symptoms (NMS), freezing of gait, and the optimal timing of DBS are still under investigation. The findings of pathological oscillations and abnormal frequency to amplitude coupling provide models to develop adaptive DBS. Transcranial magnetic stimulation (TMS) revealed abnormal cortical excitability and plasticity in PD. Consecutive sessions of high‐frequency, repetitive TMS on the motor cortex showed promising results. Paired TMS and DBS at specific times provided a novel way to investigate PD pathophysiology and have potential as a future treatment. Transcranial direct current stimulation or transcranial alternating current stimulation with multifocal electrodes or at specific phases of oscillation are also potential future strategies.

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Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial

Cited by 119 publications

References 30 publications

Different effects of levodopa and subthalamic stimulation on emotional conflict in Parkinson's disease

Different effects of levodopa and subthalamic stimulation on emotional conflict in Parkinson's disease

Cellular, molecular, and clinical mechanisms of action of deep brain stimulation—a systematic review on established indications and outlook on future developments

Invasive and Noninvasive Brain Stimulation in Parkinson's Disease: Clinical Effects and Future Perspectives

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