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1. Adaptive vs. Conventional Deep Brain Stimulation: One-Year Subthalamic Recordings and Clinical Monitoring in a Patient with Parkinson’s Disease

Author

Laura Caffi, Luigi M. Romito, Chiara Palmisano, Vanessa Aloia, Mattia Arlotti, Lorenzo Rossi, Sara Marceglia, Alberto Priori, Roberto Eleopra, Vincenzo Levi, Alberto Mazzoni, and Ioannis U. Isaias

Subjects
parkinson’s disease, adaptive deep brain stimulation, neuromodulation, subthalamic nucleus, local field potentials, biomarkers, Technology, Biology (General), QH301-705.5
Abstract

Conventional DBS (cDBS) for Parkinson’s disease uses constant, predefined stimulation parameters, while the currently available adaptive DBS (aDBS) provides the possibility of adjusting current amplitude with respect to subthalamic activity in the beta band (13–30 Hz). This preliminary study on one patient aims to describe how these two stimulation modes affect basal ganglia dynamics and, thus, behavior in the long term. We collected clinical data (UPDRS-III and -IV) and subthalamic recordings of one patient with Parkinson’s disease treated for one year with aDBS, alternated with short intervals of cDBS. Moreover, after nine months, the patient discontinued all dopaminergic drugs while keeping aDBS. Clinical benefits of aDBS were superior to those of cDBS, both with and without medications. This improvement was paralleled by larger daily fluctuations of subthalamic beta activity. Moreover, with aDBS, subthalamic beta activity decreased during asleep with respect to awake hours, while it remained stable in cDBS. These preliminary data suggest that aDBS might be more effective than cDBS in preserving the functional role of daily beta fluctuations, thus leading to superior clinical benefit. Our results open new perspectives for a restorative brain network effect of aDBS as a more physiological, bidirectional, brain–computer interface.

Published
2024
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2. 26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3

Author

Adam J. H. Newton, Alexandra H. Seidenstein, Robert A. McDougal, Alberto Pérez-Cervera, Gemma Huguet, Tere M-Seara, Caroline Haimerl, David Angulo-Garcia, Alessandro Torcini, Rosa Cossart, Arnaud Malvache, Kaoutar Skiker, Mounir Maouene, Gianmarco Ragognetti, Letizia Lorusso, Andrea Viggiano, Angelo Marcelli, Rosa Senatore, Antonio Parziale, S. Stramaglia, M. Pellicoro, L. Angelini, E. Amico, H. Aerts, J. Cortés, S. Laureys, D. Marinazzo, I. Bassez, L. Faes, Hannes Almgren, Adeel Razi, Frederik Van de Steen, Ruth Krebs, Hannelore Aerts, Lida Kanari, Pawel Dlotko, Martina Scolamiero, Ran Levi, Julian Shillcock, Christiaan P.J. de Kock, Kathryn Hess, Henry Markram, Cheng Ly, Gary Marsat, Tom Gillespie, Malin Sandström, Mathew Abrams, Jeffrey S. Grethe, Maryann Martone, Robin De Gernier, Sergio Solinas, Christian Rössert, Marc Haelterman, Serge Massar, Valentina Pasquale, Vito Paolo Pastore, Sergio Martinoia, Paolo Massobrio, Cristiano Capone, Núria Tort-Colet, Maria V. Sanchez-Vives, Maurizio Mattia, Ali Almasi, Shaun L. Cloherty, David B. Grayden, Yan T. Wong, Michael R. Ibbotson, Hamish Meffin, Luke Y. Prince, Krasimira Tsaneva-Atanasova, Jack R. Mellor, Alberto Mazzoni, Manuela Rosa, Jacopo Carpaneto, Luigi M. Romito, Alberto Priori, Silvestro Micera, Rosanna Migliore, Carmen Alina Lupascu, Francesco Franchina, Luca Leonardo Bologna, Armando Romani, Sára Saray, Werner Van Geit, Szabolcs Káli, Alex Thomson, Audrey Mercer, Sigrun Lange, Joanne Falck, Eilif Muller, Felix Schürmann, Dmitrii Todorov, Robert Capps, William Barnett, Yaroslav Molkov, Federico Devalle, Diego Pazó, Ernest Montbrió, Gabriela Mochol, Habiba Azab, Benjamin Y. Hayden, Rubén Moreno-Bote, Pragathi Priyadharsini Balasubramani, Srinivasa V. Chakravarthy, Vignayanandam R. Muddapu, Medorian D. Gheorghiu, Bartul Mimica, Jonathan Withlock, Raul C. Mureșan, Jennifer L. Zick, Kelsey Schultz, Rachael K. Blackman, Matthew V. Chafee, Theoden I. Netoff, Nicholas Roberts, Vivek Nagaraj, Andrew Lamperski, Logan L. Grado, Matthew D. Johnson, David P. Darrow, Davide Lonardoni, Hayder Amin, Stefano Di Marco, Alessandro Maccione, Luca Berdondini, Thierry Nieus, Marcel Stimberg, Dan F. M. Goodman, Thomas Nowotny, Veronika Koren, Valentin Dragoi, Klaus Obermayer, Samy Castro, Mariano Fernandez, Wael El-Deredy, Kesheng Xu, Jean Paul Maidana, Patricio Orio, Weiliang Chen, Iain Hepburn, Francesco Casalegno, Adrien Devresse, Aleksandr Ovcharenko, Fernando Pereira, Fabien Delalondre, Erik De Schutter, Peter Bratby, Andrew R. Gallimore, Guido Klingbeil, Criseida Zamora, Yunliang Zang, Patrick Crotty, Eric Palmerduca, Alberto Antonietti, Claudia Casellato, Csaba Erö, Egidio D’Angelo, Marc-Oliver Gewaltig, Alessandra Pedrocchi, Ilja Bytschok, Dominik Dold, Johannes Schemmel, Karlheinz Meier, Mihai A. Petrovici, Hui-An Shen, Simone Carlo Surace, Jean-Pascal Pfister, Baptiste Lefebvre, Olivier Marre, Pierre Yger, Athanasia Papoutsi, Jiyoung Park, Ryan Ash, Stelios Smirnakis, Panayiota Poirazi, Richard A. Felix, Alexander G. Dimitrov, Christine Portfors, Silvia Daun, Tibor I. Toth, Joanna Jędrzejewska-Szmek, Nadine Kabbani, Kim T. Blackwel, Bahar Moezzi, Natalie Schaworonkow, Lukas Plogmacher, Mitchell R. Goldsworthy, Brenton Hordacre, Mark D. McDonnell, Nicolangelo Iannella, Michael C. Ridding, Jochen Triesch, Reinoud Maex, Karen Safaryan, Volker Steuber, Rongxiang Tang, Yi-Yuan Tang, Darya V. Verveyko, Alexey R. Brazhe, Andrey Yu Verisokin, Dmitry E. Postnov, Cengiz Günay, Gabriella Panuccio, Michele Giugliano, Astrid A. Prinz, Pablo Varona, Mikhail I. Rabinovich, Jack Denham, Thomas Ranner, Netta Cohen, Maria Reva, Nelson Rebola, Tekla Kirizs, Zoltan Nusser, David DiGregorio, Eirini Mavritsaki, Panos Rentzelas, Nikul H. Ukani, Adam Tomkins, Chung-Heng Yeh, Wesley Bruning, Allison L. Fenichel, Yiyin Zhou, Yu-Chi Huang, Dorian Florescu, Carlos Luna Ortiz, Paul Richmond, Chung-Chuan Lo, Daniel Coca, Ann-Shyn Chiang, Aurel A. Lazar, Jennifer L. Creaser, Congping Lin, Peter Ashwin, Jonathan T. Brown, Thomas Ridler, Daniel Levenstein, Brendon O. Watson, György Buzsáki, John Rinzel, Rodica Curtu, Anh Nguyen, Sahand Assadzadeh, Peter A. Robinson, Paula Sanz-Leon, Caroline G. Forlim, Lírio O. B. de Almeida, Reynaldo D. Pinto, Francisco B. Rodríguez, Ángel Lareo, Caroline Garcia Forlim, Aaron Montero, Thiago Mosqueiro, Ramon Huerta, Francisco B. Rodriguez, Vinicio Changoluisa, Vinícius L. Cordeiro, César C. Ceballos, Nilton L. Kamiji, Antonio C. Roque, William W. Lytton, Andrew Knox, Joshua J. C. Rosenthal, Svitlana Popovych, Liqing Liu, Bin A. Wang, Tibor I. Tóth, Christian Grefkes, Gereon R. Fink, Nils Rosjat, Abraham Perez-Trujillo, Andres Espinal, Marco A. Sotelo-Figueroa, Ivan Cruz-Aceves, Horacio Rostro-Gonzalez, Martin Zapotocky, Martina Hoskovcová, Jana Kopecká, Olga Ulmanová, Evžen Růžička, Matthias Gärtner, Sevil Duvarci, Jochen Roeper, Gaby Schneider, Stefan Albert, Katharina Schmack, Michiel Remme, Susanne Schreiber, Michele Migliore, Carmen A. Lupascu, Luca L. Bologna, Stefano M. Antonel, Jean-Denis Courcol, Sami Utku Çelikok, Eva M. Navarro-López, Neslihan Serap Şengör, Rahmi Elibol, Neslihan Serap Sengor, Mustafa Yasir Özdemir, Tianyi Li, Angelo Arleo, Denis Sheynikhovich, Akihiro Nakamura, Masanori Shimono, Youngjo Song, Sol Park, Ilhwan Choi, Jaeseung Jeong, Hee-sup Shin, Sadra Sadeh, Padraig Gleeson, R. Angus Silver, Alexandra Pierri Chatzikalymniou, Frances K. Skinner, Lazaro M. Sanchez-Rodriguez, Roberto C. Sotero, Loreen Hertäg, Owen Mackwood, Henning Sprekeler, Steffen Puhlmann, Simon N. Weber, David Higgins, Laura B. Naumann, Ramakrisnan Iyer, Stefan Mihalas, Valentina Ticcinelli, Tomislav Stankovski, Peter V. E. McClintock, Aneta Stefanovska, Predrag Janjić, Dimitar Solev, Gerald Seifert, Ljupčo Kocarev, Christian Steinhäuser, Mehrdad Salmasi, Stefan Glasauer, Martin Stemmler, Danke Zhang, Chi Zhang, Armen Stepanyants, Julia Goncharenko, Lieke Kros, Neil Davey, Chris de Zeeuw, Freek Hoebeek, Ankur Sinha, Roderick Adams, Michael Schmuker, Maria Psarrou, Maria Schilstra, Benjamin Torben-Nielsen, Christoph Metzner, Achim Schweikard, Tuomo Mäki-Marttunen, Bartosz Zurowski, Daniele Marinazzo, Luca Faes, Sebastiano Stramaglia, Henry O. C. Jordan, Simon M. Stringer, Elżbieta Gajewska-Dendek, Piotr Suffczyński, Nicoladie Tam, George Zouridakis, Luca Pollonini, Mojtaba Madadi Asl, Alireza Valizadeh, Peter A. Tass, Andreas Nold, Wei Fan, Sara Konrad, Heiko Endle, Johannes Vogt, Tatjana Tchumatchenko, Juliane Herpich, Christian Tetzlaff, Jannik Luboeinski, Timo Nachstedt, Manuel Ciba, Andreas Bahmer, Christiane Thielemann, Eric S. Kuebler, Joseph S. Tauskela, Jean-Philippe Thivierge, Rembrandt Bakker, María García-Amado, Marian Evangelio, Francisco Clascá, Paul Tiesinga, Christopher L. Buckley, Taro Toyoizumi, Alexis M. Dubreuil, Rémi Monasson, Alessandro Treves, Davide Spalla, Sophie Rosay, Florence I. Kleberg, Willy Wong, Bruno de Oliveira Floriano, Toshihiko Matsuo, Tetsuya Uchida, Domenica Dibenedetto, Kâmil Uludağ, Abdorreza Goodarzinick, Maximilian Schmidt, Claus C. Hilgetag, Markus Diesmann, Sacha J. van Albada, Michael Fauth, Mark van Rossum, Manuel Reyes-Sánchez, Rodrigo Amaducci, Carlos Muñiz, Irene Elices, David Arroyo, Rafael Levi, Ben Cohen, Carson Chow, Shashaank Vattikuti, Elena Bertolotti, Raffaella Burioni, Matteo di Volo, Alessandro Vezzani, Bayar Menzat, Tim P. Vogels, Nobuhiko Wagatsuma, Susmita Saha, Reena Kapoor, Robert Kerr, John Wagner, Luis C. Garcia del Molino, Guangyu Robert Yang, Jorge F. Mejias, Xiao-Jing Wang, Hanbing Song, Joseph Goodliffe, Jennifer Luebke, Christina M. Weaver, John Thomas, Nishant Sinha, Nikhita Shaju, Tomasz Maszczyk, Jing Jin, Sydney S. Cash, Justin Dauwels, M. Brandon Westover, Maryam Karimian, Michelle Moerel, Peter De Weerd, Thomas Burwick, Ronald L. Westra, Romesh Abeysuriya, Jonathan Hadida, Stamatios Sotiropoulos, Saad Jbabdi, Mark Woolrich, Chama Bensmail, Borys Wrobel, Xiaolong Zhou, Zilong Ji, Xiao Liu, Yan Xia, Si Wu, Xiao Wang, Mingsha Zhang, Netanel Ofer, Orit Shefi, Gur Yaari, Ted Carnevale, Amit Majumdar, Subhashini Sivagnanam, Kenneth Yoshimoto, Elena Y. Smirnova, Dmitry V. Amakhin, Sergey L. Malkin, Aleksey V. Zaitsev, Anton V. Chizhov, Margarita Zaleshina, Alexander Zaleshin, Victor J. Barranca, George Zhu, Quinton M. Skilling, Daniel Maruyama, Nicolette Ognjanovski, Sara J. Aton, Michal Zochowski, Jiaxing Wu, Sara Aton, Scott Rich, Victoria Booth, Maral Budak, Salvador Dura-Bernal, Samuel A. Neymotin, Benjamin A. Suter, Gordon M. G. Shepherd, Melvin A. Felton, Alfred B. Yu, David L. Boothe, Kelvin S. Oie, Piotr J. Franaszczuk, Sergey A. Shuvaev, Batuhan Başerdem, Anthony Zador, Alexei A. Koulakov, Víctor J. López-Madrona, Ernesto Pereda, Claudio R. Mirasso, Santiago Canals, Stefano Masoli, Udaya B. Rongala, Anton Spanne, Henrik Jorntell, Calogero M. Oddo, Alexander V. Vartanov, Anastasia K. Neklyudova, Stanislav A. Kozlovskiy, Andrey A. Kiselnikov, Julia A. Marakshina, Maria Teleńczuk, Bartosz Teleńczuk, Alain Destexhe, Paula T. Kuokkanen, Anna Kraemer, Thomas McColgan, Catherine E. Carr, and Richard Kempter

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Published
2017
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3. Segregating the Frontal Cortex with Deep Brain Stimulation

Author

Barbara Hollunder, Jill L. Ostrem, Ilkem Aysu Sahin, Nanditha Rajamani, Simón Oxenford, Konstantin Butenko, Mircea Polosan, Harith Akram, Matteo Vissani, Chencheng Zhang, Bomin Sun, Martin M. Reich, Jens Volkmann, Carsten Finke, Andrea A. Kühn, Hagai Bergman, Mahlon R. DeLong, Alberto Mazzoni, Luigi M. Romito, Ludvic Zrinzo, Eileen M. Joyce, Stephan Chabardes, Philip A. Starr, Ningfei Li, and Andreas Horn

Subjects
Article
Abstract

The frontal cortex is involved in motor, cognitive, and affective brain functions. In humans, however, neuroanatomy-function mappings are predominantly derived from correlative neuroimaging studies. Hence, exactly which frontal domainscausallymediate which function remains largely elusive. Herein, we leverage a strategy that allows for causal inference using invasive neuromodulation. Studying 394 subthalamic deep brain stimulation electrodes in patients suffering from one of four brain disorders, we segregated the frontal cortex into cortical projection sites of modulated circuits by their involvement in specific functions. Modulating projections from sensory and motor cortices in dystonia, from primary motor cortex in Tourette’s syndrome, from supplementary motor cortex in Parkinson’s disease, and from ventromedial prefrontal, anterior cingulate, dorsolateral prefrontal and orbitofrontal cortices in obsessive-compulsive disorder linked to respective symptom improvements. Our findings showcase the combination of deep brain stimulation and brain connectomics as a tool for causal inference on structure-function mappings within the human brain.

Published
2023
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4. Dystonia as a prominent feature of TCF20-associated neurodevelopmental disorder: Expanding the phenotype

Author

Tatiana Svorenova, Luigi M. Romito, Isabel Colangelo, Vladimir Han, Robert Jech, Holger Prokisch, Juliane Winkelmann, Matej Skorvanek, Barbara Garavaglia, and Michael Zech

Subjects
Dystonia, Phenotype, Neurology, Dystonic Disorders, Neurodevelopmental Disorders, Humans, Neurology (clinical), Geriatrics and Gerontology, Transcription Factors
Published
2022
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5. Variants in ATP5F1B are associated with dominantly inherited dystonia

Author

Alessia Nasca, Niccolò E Mencacci, Federica Invernizzi, Michael Zech, Ignacio J Keller Sarmiento, Andrea Legati, Chiara Frascarelli, Bernabe I Bustos, Luigi M Romito, Dimitri Krainc, Juliane Winkelmann, Miryam Carecchio, Nardo Nardocci, Giovanna Zorzi, Holger Prokisch, Steven J Lubbe, Barbara Garavaglia, and Daniele Ghezzi

Subjects
ATP5F1B, case report, dystonia, incomplete penetrance, mitochondrial ATP synthase, Neurology (clinical)
Abstract

ATP5F1B is a subunit of the mitochondrial ATP synthase or complex V of the mitochondrial respiratory chain. Pathogenic variants in nuclear genes encoding assembly factors or structural subunits are associated with complex V deficiency, typically characterized by autosomal recessive inheritance and multisystem phenotypes. Movement disorders have been described in a subset of cases carrying autosomal dominant variants in structural subunits genes ATP5F1A and ATP5MC3. Here, we report the identification of two different ATP5F1B missense variants (c.1000A>C; p.Thr334Pro and c.1445T>C; p.Val482Ala) segregating with early-onset isolated dystonia in two families, both with autosomal dominant mode of inheritance and incomplete penetrance. Functional studies in mutant fibroblasts revealed no decrease of ATP5F1B protein amount but severe reduction of complex V activity and impaired mitochondrial membrane potential, suggesting a dominant-negative effect. In conclusion, our study describes a new candidate gene associated with isolated dystonia and confirms that heterozygous variants in genes encoding subunits of the mitochondrial ATP synthase may cause autosomal dominant isolated dystonia with incomplete penetrance, likely through a dominant-negative mechanism.

Published
2023

6. AOPEP variants as a novel cause of recessive dystonia: Generalized dystonia and dystonia-parkinsonism

Author

Barbara Garavaglia, Sadeq Vallian, Luigi M. Romito, Giulia Straccia, Marianna Capecci, Federica Invernizzi, Elisa Andrenelli, Arezu Kazemi, Sylvia Boesch, Robert Kopajtich, Nahid Olfati, Mohammad Shariati, Ali Shoeibi, Ariane Sadr-Nabavi, Holger Prokisch, Juliane Winkelmann, and Michael Zech

Subjects
Dystonia, Neurology, Parkinsonian Disorders, Dystonic Disorders, Mutation, Humans, Neurology (clinical), Geriatrics and Gerontology, Iran, Child, Aminopeptidases, Pedigree
Abstract

The genetic basis of autosomal-recessive dystonia remains poorly understood. Our objective was to report identification of additional individuals with variants in AOPEP, a recently described gene for recessively inherited dystonic disorders (OMIM:619565).Ongoing analysis on a high-throughput genetic platform and international case-recruitment efforts were undertaken.Novel biallelic, likely pathogenic loss-of-function alleles were identified in two pedigrees of different ethnic background. Two members of a consanguineous Iranian family shared a homozygous c.1917-1GA essential splice-site variant and featured presentations of adolescence-onset generalized dystonia. An individual of Chinese descent, homozygous for the nonsense variant c.1909GT (p.Glu637*), displayed childhood-onset generalized dystonia combined with later-manifesting parkinsonism. One additional Iranian patient with adolescence-onset generalized dystonia carried an ultrarare, likely protein-damaging homozygous missense variant (c.1201CT [p.Arg401Trp]).These findings support the implication of AOPEP in recessive forms of generalized dystonia and dystonia-parkinsonism. Biallelic AOPEP variants represent a worldwide cause of dystonic movement-disorder phenotypes and should be considered in dystonia molecular testing approaches.

Published
2022

7. Cerebrospinal fluid neuropathological biomarkers in beta-propeller protein-associated neurodegeneration, with complicated parkinsonian phenotype

Author

Roberta Bonomo, Antonio E. Elia, Roberto Cilia, Luigi M. Romito, Nico Golfrè Andreasi, Grazia Devigili, Salvatore Bonvegna, Giulia Straccia, Barbara Garavaglia, Celeste Panteghini, Roberto Eleopra, Bonomo, R, Elia, A, Cilia, R, Romito, L, Golfrè Andreasi, N, Devigili, G, Bonvegna, S, Straccia, G, Garavaglia, B, Panteghini, C, and Eleopra, R

Subjects
Phenotype, Neurology, BPAN, WDR45, Neuroaxonal Dystrophies, Humans, Neurology (clinical), Biomarker, Geriatrics and Gerontology, Iron Metabolism Disorders, Beta-propeller protein-associated neurodegeneration, Biomarkers, Neuropathology
Published
2022

9. Quantitative gait analysis in parkin disease: Possible role of dystonia

Author

Anna, Castagna, Serena, Frittoli, Maurizio, Ferrarin, Francesca, Del Sorbo, Luigi M, Romito, Antonio E, Elia, and Alberto, Albanese

Subjects
Adult, Male, Ubiquitin-Protein Ligases, dystonia, gait analysis, kinematics, kinetics, parkin disease, Neurology, Neurology (clinical), Parkinson Disease, Middle Aged, Biomechanical Phenomena, Settore MED/26 - NEUROLOGIA, Humans, Female, Gait Disorders, Neurologic
Abstract

Parkin disease (PARK2, OMIM 602544) is an autosomal-recessive early-onset parkinsonism characterized by an early occurrence of lower limb dystonia. The aim of this study was to analyze spatiotemporal, kinematic, and kinetic gait parameters in patients with parkin disease in the OFF and ON conditions compared to healthy age-matched controls.Fifteen patients with parkin disease and 15 healthy age-matched controls were studied in a gait analysis laboratory with an integrated optoelectronic system. Spatiotemporal, kinematic, and kinetic gait parameters at a self-selected speed were recorded in the OFF and ON conditions. A jerk index was computed to quantify the possible reduction of smoothness of joint movements.Compared to controls, parkin patients had, either in the OFF or in the ON conditions, significant reduction of walking velocity, increased step width, and decreased percentage of double support. Kinematic analysis in both conditions showed: increased ankle dorsiflexion and knee flexion at the initial contact; maximal flexion and increased range of motion in mid stance; increased hip flexion and max extension in stance at pelvis; and increased mean tilt antiversion. Kinetics showed increased hip and knee power generation in stance in either condition. The jerk index was increased at all joints both in OFF and ON. There were no correlations between individual gait parameters and clinical ratings.Parkin patients have an abnormal gait pattern that does not vary between the OFF and the ON conditions. Variations recorded with instrumented analysis are more evident for kinematic than kinetic parameters at lower limbs. Severity of dystonia does not correlate with any individual kinematic parameter. © 2016 International Parkinson and Movement Disorder Society.

Published
2016

10. Replacement of dopaminergic medication with subthalamic nucleus stimulation in Parkinson's disease: long-term observation

Author

Luigi M, Romito, Maria Fiorella, Contarino, Nicola, Vanacore, Anna Rita, Bentivoglio, Massimo, Scerrati, Alberto, Albanese, and Neurology

Subjects
Male, Time Factors, Deep Brain Stimulation, Dopamine Agents, Parkinson Disease, Motor Activity, Severity of Illness Index, Electrodes, Implanted, Levodopa, Disability Evaluation, Settore MED/26 - NEUROLOGIA, Treatment Outcome, Subthalamic Nucleus, Humans, Female, Longitudinal Studies
Abstract

Stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease (PD), but the medication requirements after implant are poorly known. We performed a long-term prospective evaluation of 20 patients maintained at stable dopaminergic therapy for 5 years after bilateral STN implants, who were evaluated 6 months, 1 year, 3 years, and 5 years after surgery. We measured, during the entire observation period, the effect of deep brain stimulation on motor and functional outcome measures, the levodopa equivalent daily dose and the total electrical energy delivered. At 5 years, the UPDRS motor score had improved by 54.2% and levodopa equivalent dose was reduced by 61.9%, compared with preimplant. Dopaminergic medication remained stable during the observation period, but energy was progressively increased over time. Rest tremor, rigidity, gait, lower and upper limb akinesia, and total axial score were improved in decreasing order. Postural stability and speech improved transiently, whereas on-period freezing of gait, motor fluctuations and dyskinesias recovered durably. Functional measures did not show improvement in autonomy and daily living activities after STN implant. Chronic STN stimulation allows to replace for dopaminergic medications in the long-term at the expense of an increase of the total energy delivered. This is associated with marked improvement of motor features without a matching benefit in functional measures.

Published
2009

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