Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry

Jukka Peltola; Albert J Colon; José Pimentel; Volker A Coenen; Antonio Gil-Nagel; Antonio Gonçalves Ferreira; Kai Lehtimäki; Philippe Ryvlin; Rod S Taylor; Linda Ackermans; Jacqueline Ardesch; Carla Bentes; Magdalena Bosak; Jorge G Burneo; Clara Chamadoira; Christian E Elger; Loránd Erőss; Dániel Fabo; Howard Faulkner; Jacek Gawlowicz; Alireza Gharabaghi; Maurizio Iacoangeli; Jozsef Janszky; Soila Järvenpää; Elisabeth Kaufmann; Kuan H Kho; Eva Kumlien; Helmut Laufs; Christian Lettieri; Paulo Linhares; Soheyl Noachtar; Andrew Parrent; Ekaterina Pataraia; Nikunj K Patel; Ana Rita Peralta; Attila Rácz; Alexandre Rainha Campos; Ricardo Rego; Riccardo A Ricciuti; Sabine Rona; Rob P W Rouhl; Andreas Schulze-Bonhage; Rick Schuurman; Mathieu Sprengers; Albert Sufianov; Yasin Temel; Tom Theys; Wim Van Paesschen; Dirk Van Roost; Rui Vaz; Kristl Vonck; Louis Wagner; Jack Zwemmer; Abdallah Abouihia; Thomas C Brionne; Frans Gielen; Paul A J M Boon; MORE Study Group

doi:10.1212/WNL.0000000000206887

Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry

Neurology. 2023 May 2;100(18):e1852-e1865. doi: 10.1212/WNL.0000000000206887. Epub 2023 Mar 16.

Authors

Jukka Peltola¹, Albert J Colon², José Pimentel², Volker A Coenen², Antonio Gil-Nagel², Antonio Gonçalves Ferreira², Kai Lehtimäki², Philippe Ryvlin², Rod S Taylor², Linda Ackermans², Jacqueline Ardesch², Carla Bentes², Magdalena Bosak², Jorge G Burneo², Clara Chamadoira², Christian E Elger², Loránd Erőss², Dániel Fabo², Howard Faulkner², Jacek Gawlowicz², Alireza Gharabaghi², Maurizio Iacoangeli², Jozsef Janszky², Soila Järvenpää², Elisabeth Kaufmann², Kuan H Kho², Eva Kumlien², Helmut Laufs², Christian Lettieri², Paulo Linhares², Soheyl Noachtar², Andrew Parrent², Ekaterina Pataraia², Nikunj K Patel², Ana Rita Peralta², Attila Rácz², Alexandre Rainha Campos², Ricardo Rego², Riccardo A Ricciuti², Sabine Rona², Rob P W Rouhl², Andreas Schulze-Bonhage², Rick Schuurman², Mathieu Sprengers², Albert Sufianov², Yasin Temel², Tom Theys², Wim Van Paesschen², Dirk Van Roost², Rui Vaz², Kristl Vonck², Louis Wagner², Jack Zwemmer², Abdallah Abouihia², Thomas C Brionne², Frans Gielen², Paul A J M Boon²; MORE Study Group

Collaborators

Affiliations

¹ From the Department of Neurology (J. Peltola, S.J.), Tampere University and Tampere University Hospital, Finland; Academic Center for Epileptology Kempenhaeghe/MUMC+ (A.J.C., L.A., R.P.W.R., L.W.), Maastricht, the Netherlands; Department of Neurosciences and Mental Health (J. Pimentel), Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Portugal; Department of Stereotactic and Functional Neurosurgery (V.A.C.), Universitätsklinikum Freiburg, Germany; Neurology Department (A.G.-N.), Epilepsy Program, Hospital Ruber Internacional, Madrid, Spain; Department of Neurosurgery (A.G.F., A.R.C.), Hospital Santa Maria Centro Hospitalar Lisboa Norte, Portugal; Department of Neurosurgery (K.L.), Tampere University Hospital and Tampere University, Finland; Département des Neurosciences Cliniques (P.R.), centre hospitalier universitaire vaudois (CHUV), Lausanne, Switzerland; MRC/CSO Social and Public Health Sciences Unit & Robertson Centre for Biostatistics (R.S.T.), Institute of Health and Well Being, University of Glasgow; College of Medicine and Health (R.S.T.), University of Exeter, United Kingdom; Departments of Neurosurgery (L.A., Y.T.), Maastricht University Medical Center, the Netherlands; Stichting Epilepsie Instellingen Nederland (SEIN) (J.A.), Zwolle; Neurophysiology Monitoring Unit (C.B.), Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte; Faculdade de Medicina (C.B., A.R.P.), Universidade de Lisboa, Portugal; Department of Neurology (M.B.), Jagiellonian University Medical College, Faculty of Medicine, Krakow, Poland; Western University (J.G.B., A.P.), London, Ontario, Canada; Neurosurgery Department (C.C., P.L., R.V.), Centro Hospitalar Universitário de São João, Porto, Portugal; Department of Epileptology (C.E.E., A.R.), University Hospital Bonn, Germany; National Institute of Clinical Neuroscience (L.E.); Országos Idegtudományi Intézet/National Institute of Neurosciences (D.F.), Budapest, Hungary; North Bristol NHS Trust (H.F.), Bristol, United Kingdom; Wojewodzki Szpital Specjalistyczny w Lublinie (J.G.), Poland; Institute for Neuromodulation and Neurotechnology (A.G.), Department of Neurosurgery and Neurotechnology, University of Tübingen, Germany; Department of Neurosurgery (M.I.), Umberto I General University Hospital, Università Politecnica delle Marche, Ancona, Italy; Department of Neurology (J.J.), Medical School, University of Pécs, Hungary; Department of Neurology (E. Kaufmann), Ludwig Maximilians University, Munich, Germany; Medisch Spectrum Twente (MST) (K.H.K.), Enschede, the Netherlands; Department of Neuroscience (E. Kumlien), Uppsala University, Sweden; Klinik für Neurologie (H.L.), Universitätsklinikum Schleswig-Holstein, Campus Kiel, Christian-Albrechts-Universität zu Kiel, Germany; Neurology and Clinical Neurophysiology Unit (C.L.), Department of Neuroscience, "S. Maria della Misericordia" University Hospital, Udine, Italy; Klinikum der Universität München (S.N.), Großhadern Neurologische Klinik und Poliklinik, Germany; Medizinische Universität Wien (E.P.), Austria; Southmead Hospital (N.K.P.), North Bristol NHS Trust, United Kingdom; Laboratory of EEG/Sleep (A.R.P.), Department of Neurology, Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Portugal; Neurophysiology Unit (R.R.), Neurology Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Department of Neurosurgery (R.A.R.), Viterbo Hospital, Italy; Epilepsy Unit (S.R.), Department of Neurosurgery and Neurotechnology, University of Tübingen, Germany; Department of Neurology (R.P.W.R.), Maastricht University Medical Centre+; School for Mental Health and Neurosciences (R.P.W.R.), Maastricht University, the Netherlands; University Hospital Freiburg (A.S.-B.), Germany; Amsterdam University Medical Center (R.S.), the Netherlands; Department of Neurology (M.S.), Ghent University Hospital, Ghent University, Belgium; Federal Centre of Neurosurgery (Tyumen) (A.S.), I.M. Sechenov First Moscow State Medical University, Moscow, Russia; UZ Leuven (T.T.); Department of Neurology (W.V.P.), UZ Leuven; Laboratory for Epilepsy Research (W.V.P.), KU Leuven; Department of Neurosurgery (D.V.R.), and Department of Neurology (K.V., P.A.J.M.B.), Ghent University Hospital, Ghent University, Belgium; Stichting Epilepsie Instellingen Nederland (SEIN) (J.Z.), Heemstede; Clinical Department (A.A., T.C.B.), Medtronic Internal Trading Sàrl, Tolochenaz, Switzerland; and Medtronic Bakken Research Center (F.G.), Maastricht, the Netherlands. jukka.peltola@tuni.fi.
² From the Department of Neurology (J. Peltola, S.J.), Tampere University and Tampere University Hospital, Finland; Academic Center for Epileptology Kempenhaeghe/MUMC+ (A.J.C., L.A., R.P.W.R., L.W.), Maastricht, the Netherlands; Department of Neurosciences and Mental Health (J. Pimentel), Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Portugal; Department of Stereotactic and Functional Neurosurgery (V.A.C.), Universitätsklinikum Freiburg, Germany; Neurology Department (A.G.-N.), Epilepsy Program, Hospital Ruber Internacional, Madrid, Spain; Department of Neurosurgery (A.G.F., A.R.C.), Hospital Santa Maria Centro Hospitalar Lisboa Norte, Portugal; Department of Neurosurgery (K.L.), Tampere University Hospital and Tampere University, Finland; Département des Neurosciences Cliniques (P.R.), centre hospitalier universitaire vaudois (CHUV), Lausanne, Switzerland; MRC/CSO Social and Public Health Sciences Unit & Robertson Centre for Biostatistics (R.S.T.), Institute of Health and Well Being, University of Glasgow; College of Medicine and Health (R.S.T.), University of Exeter, United Kingdom; Departments of Neurosurgery (L.A., Y.T.), Maastricht University Medical Center, the Netherlands; Stichting Epilepsie Instellingen Nederland (SEIN) (J.A.), Zwolle; Neurophysiology Monitoring Unit (C.B.), Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte; Faculdade de Medicina (C.B., A.R.P.), Universidade de Lisboa, Portugal; Department of Neurology (M.B.), Jagiellonian University Medical College, Faculty of Medicine, Krakow, Poland; Western University (J.G.B., A.P.), London, Ontario, Canada; Neurosurgery Department (C.C., P.L., R.V.), Centro Hospitalar Universitário de São João, Porto, Portugal; Department of Epileptology (C.E.E., A.R.), University Hospital Bonn, Germany; National Institute of Clinical Neuroscience (L.E.); Országos Idegtudományi Intézet/National Institute of Neurosciences (D.F.), Budapest, Hungary; North Bristol NHS Trust (H.F.), Bristol, United Kingdom; Wojewodzki Szpital Specjalistyczny w Lublinie (J.G.), Poland; Institute for Neuromodulation and Neurotechnology (A.G.), Department of Neurosurgery and Neurotechnology, University of Tübingen, Germany; Department of Neurosurgery (M.I.), Umberto I General University Hospital, Università Politecnica delle Marche, Ancona, Italy; Department of Neurology (J.J.), Medical School, University of Pécs, Hungary; Department of Neurology (E. Kaufmann), Ludwig Maximilians University, Munich, Germany; Medisch Spectrum Twente (MST) (K.H.K.), Enschede, the Netherlands; Department of Neuroscience (E. Kumlien), Uppsala University, Sweden; Klinik für Neurologie (H.L.), Universitätsklinikum Schleswig-Holstein, Campus Kiel, Christian-Albrechts-Universität zu Kiel, Germany; Neurology and Clinical Neurophysiology Unit (C.L.), Department of Neuroscience, "S. Maria della Misericordia" University Hospital, Udine, Italy; Klinikum der Universität München (S.N.), Großhadern Neurologische Klinik und Poliklinik, Germany; Medizinische Universität Wien (E.P.), Austria; Southmead Hospital (N.K.P.), North Bristol NHS Trust, United Kingdom; Laboratory of EEG/Sleep (A.R.P.), Department of Neurology, Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Portugal; Neurophysiology Unit (R.R.), Neurology Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Department of Neurosurgery (R.A.R.), Viterbo Hospital, Italy; Epilepsy Unit (S.R.), Department of Neurosurgery and Neurotechnology, University of Tübingen, Germany; Department of Neurology (R.P.W.R.), Maastricht University Medical Centre+; School for Mental Health and Neurosciences (R.P.W.R.), Maastricht University, the Netherlands; University Hospital Freiburg (A.S.-B.), Germany; Amsterdam University Medical Center (R.S.), the Netherlands; Department of Neurology (M.S.), Ghent University Hospital, Ghent University, Belgium; Federal Centre of Neurosurgery (Tyumen) (A.S.), I.M. Sechenov First Moscow State Medical University, Moscow, Russia; UZ Leuven (T.T.); Department of Neurology (W.V.P.), UZ Leuven; Laboratory for Epilepsy Research (W.V.P.), KU Leuven; Department of Neurosurgery (D.V.R.), and Department of Neurology (K.V., P.A.J.M.B.), Ghent University Hospital, Ghent University, Belgium; Stichting Epilepsie Instellingen Nederland (SEIN) (J.Z.), Heemstede; Clinical Department (A.A., T.C.B.), Medtronic Internal Trading Sàrl, Tolochenaz, Switzerland; and Medtronic Bakken Research Center (F.G.), Maastricht, the Netherlands.

Abstract

Background and objectives: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice.

Methods: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes.

Results: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported.

Discussion: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation.

Classification of evidence: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy.

Trial registration information: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

Publication types

Randomized Controlled Trial
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Anterior Thalamic Nuclei*
Child
Deep Brain Stimulation* / adverse effects
Drug Resistant Epilepsy* / therapy
Epilepsy* / etiology
Female
Humans
Male
Prospective Studies
Quality of Life
Registries
Retrospective Studies
Seizures / etiology
Thalamus

Associated data

ClinicalTrials.gov/NCT01521754