丘脑前核深部脑刺激治疗耐药性癫痫的 MORE 多中心患者注册研究。
Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.
机构信息
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.
出版信息
Neurology. 2023 May 2;100(18):e1852-e1865. doi: 10.1212/WNL.0000000000206887. Epub 2023 Mar 16.
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 ( < 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 ( < 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.
背景与目的
在前丘脑核（ANT DBS）深部脑刺激治疗耐药性癫痫（DRE）的双盲刺激丘脑前部治疗癫痫随机对照试验中，证明了 ANT DBS 在患者中的疗效。美敦力癫痫登记处（MORE）旨在了解 ANT DBS 治疗在常规临床实践中的安全性和更长期疗效。
方法
MORE 是一个收集前瞻性和回顾性临床数据的观察性登记处。参与者年龄至少为 18 岁，招募了来自 13 个国家的 25 个中心的局灶性 DRE 患者。他们在至少 2 年内接受了癫痫发作频率（SF）、反应率（RR）、健康相关生活质量（癫痫生活质量量表 31 项）、抑郁和安全性结果的随访。
结果
191 名入组患者中，170 名（平均[SD]年龄 35.6[10.7]岁，43%为女性）接受了 DBS 治疗，并符合所有入选标准。在基线时，38%的患者报告存在认知障碍。从基线的每月 15.8 次癫痫发作到 2 年时的每月 8.8 次癫痫发作（<0.0001），中位数每月 SF 降低了 33.1%，RR 为 32.3%。在完成 5 年随访的 47 名患者亚组中，从基线时的每月 16 次癫痫发作到 5 年时的每月 7.9 次癫痫发作（<0.0001），中位数每月 SF 降低了 55.1%，RR 为 53.2%。与低容量中心相比，高容量中心（>10 例植入）在 2 年内 SF 的中位数每月降低了 42.8%。在认知障碍患者中，与无认知障碍患者相比，2 年内 SF 的中位数每月降低了 26.0%。最常报告的不良事件是癫痫发作（16%）、记忆障碍（患者报告的抱怨，15%）、抑郁情绪（患者报告的抱怨，13%）和癫痫（12%）的变化（如发作频率/严重程度增加）。报告了一例确诊的癫痫猝死病例。
讨论
MORE 登记处支持在植入后 2 年内，ANT DBS 治疗在现实环境中的有效性和安全性。
证据分类
这项研究提供了 IV 级证据，表明 ANT DBS 可降低耐药性局灶性癫痫患者的癫痫发作频率。
试验注册信息
MORE ClinicalTrials.gov 标识符：NCT01521754，于 2012 年 1 月 31 日首次发布。
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