伴失神的眼睑肌阵挛患者的电临床特征及长期癫痫发作结局
Electroclinical Features and Long-term Seizure Outcome in Patients With Eyelid Myoclonia With Absences.
作者信息
Cerulli Irelli Emanuele, Cocchi Enrico, Ramantani Georgia, Caraballo Roberto H, Giuliano Loretta, Yilmaz Tulay, Morano Alessandra, Panagiotakaki Eleni, Operto Francesca F, Gonzalez Giraldez Beatriz, Silvennoinen Katri, Casciato Sara, Comajuan Marion, Balestrini Simona, Fortunato Francesco, Coppola Antonietta, Di Gennaro Giancarlo, Labate Angelo, Sofia Vito, Kluger Gerhard J, Kasteleijn-Nolst Trenité Dorothée G A, Gambardella Antonio, Baykan Betul, Sisodiya Sanjay M, Arzimanoglou Alexis, Striano Pasquale, Di Bonaventura Carlo
机构信息
From the Department of Human Neurosciences (E.C.I., A.M., C.D.B.), Sapienza, University of Rome, Italy; Department of Precision Medicine and Genomics (E.C.), Department of Medicine, Columbia University, New York, NY; Department of Neuropediatrics (G.R.), University Children's Hospital Zurich, Switzerland; Department of Neurology (R.H.C.), Hospital de Pediatría "Prof. Dr. Juan P Garrahan," Buenos Aires, Argentina; Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia" (L.G., V.S.), Section of Neurosciences, University of Catania, Italy; Departments of Neurology and Clinical Neurophysiology (T.Y., B.B.), Istanbul University, Istanbul Faculty of Medicine, Turkey; Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology (E.P., M.C., A.A.), University Hospitals of Lyon (HCL), member of the ERN EpiCARE, France; Child and Adolescent Neuropsychiatry Unit (F.F.O.), Department of Medicine, Surgery and Dentistry, University of Salerno, Italy; Epilepsy Unit (B.G.G.), Neurology Service, Hospital Universitario and IIS Fundación Jiménez Díaz and CIBERER, Madrid, Spain; Department of Clinical and Experimental Epilepsy (S.B., K.S., S.M.S.), UCL Queen Square Institute of Neurology, London, UK; IRCCS NEUROMED (S.C., G.D.G.), Pozzilli, Isernia, Italy; Institute of Neurology (S.B.), UCL, London, UK; Institute of Neurology (F.F., A.L., A.G.), University Magna Graecia, Catanzaro, Italy; Department of Neuroscience and Reproductive and Odontostomatological Sciences (A.C.), Federico II University, Naples, Italy; Clinic for Neuropediatrics and Neurorehabilitation (G.J.K.), Epilepsy Center for Children and Adolescents, Schoen Clinic Vogtareuth, Germany; Department of Neurosurgery and Epilepsy (D.G.A.K.-N.T.), University Medical Center, Utrecht University, the Netherlands; and Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS "Istituto Giannina Gaslini," Genova, Italy.
出版信息
Neurology. 2022 May 3;98(18):e1865-e1876. doi: 10.1212/WNL.0000000000200165. Epub 2022 Mar 15.
BACKGROUND AND OBJECTIVES
Eyelid myoclonia (EM) with absences (EMA) is a generalized epilepsy syndrome with a prognosis and clinical characteristics that are still partially undefined. We investigated electroclinical endophenotypes and long-term seizure outcome in a large cohort of patients with EMA.
METHODS
In this multicenter retrospective study, patients with EMA with ≥5 years of follow-up were included. We investigated prognostic patterns and sustained terminal remission (STR), along with their prognostic factors. Moreover, a 2-step cluster analysis was used to investigate the presence of distinct EMA endophenotypes.
RESULTS
We included 172 patients with a median age at onset of 7 years (interquartile range [IQR] 5-10 years) and a median follow-up duration of 14 years (IQR 8.25-23.75 years). Sixty-six patients (38.4%) displayed a nonremission pattern, whereas remission and relapse patterns were encountered in 56 (32.6%) and 50 (29.1%) participants. Early epilepsy onset, history of febrile seizures (FS), and EM status epilepticus significantly predicted a nonremission pattern according to multinomial logistic regression analysis. STR was achieved by 68 (39.5%) patients with a mean latency of 14.05 years (SD ±12.47 years). Early epilepsy onset, psychiatric comorbid conditions, and a history of FS and generalized tonic-clonic seizures were associated with a lower probability of achieving STR according to a Cox regression proportional hazards model. Antiseizure medication (ASM) withdrawal was attempted in 62 of 172 patients, and seizures recurred in 74.2%. Cluster analysis revealed 2 distinct clusters with 86 patients each. Cluster 2, which we defined as EMA-plus, was characterized by an earlier age at epilepsy onset, higher rate of intellectual disability, EM status epilepticus, generalized paroxysmal fast activity, self-induced seizures, FS, and poor ASM response, whereas cluster 1, the EMA-only cluster, was characterized by a higher rate of seizure remission and more favorable neuropsychiatric outcome.
DISCUSSION
Early epilepsy onset was the most relevant prognostic factor for poor treatment response. A long latency between epilepsy onset and ASM response was observed, suggesting the effect of age-related brain changes in EMA remission. Last, our cluster analysis showed a clear-cut distinction of patients with EMA into an EMA-plus insidious subphenotype and an EMA-only benign cluster that strongly differed in terms of remission rates and cognitive outcomes.
背景与目的
伴失神的眼睑肌阵挛（EMA）是一种全身性癫痫综合征，其预后和临床特征仍部分不明确。我们调查了一大群EMA患者的电临床内表型和长期癫痫发作结局。
方法
在这项多中心回顾性研究中，纳入了随访时间≥5年的EMA患者。我们调查了预后模式和持续终末期缓解（STR）及其预后因素。此外，采用两步聚类分析来研究是否存在不同的EMA内表型。
结果
我们纳入了172例患者，发病年龄中位数为7岁（四分位间距[IQR]5 - 10岁），随访时间中位数为14年（IQR 8.25 - 23.75年）。66例患者（38.4%）表现为未缓解模式，而56例（32.6%）和50例（29.1%）参与者出现缓解和复发模式。根据多项逻辑回归分析，癫痫发作早发、热性惊厥（FS）病史和EMA癫痫持续状态显著预测未缓解模式。68例（39.5%）患者实现了STR，平均潜伏期为14.05年（标准差±12.47年）。根据Cox回归比例风险模型，癫痫发作早发、精神科合并症以及FS和全身强直 - 阵挛发作病史与实现STR的概率较低相关。172例患者中有62例尝试停用抗癫痫药物（ASM），74.2%的患者癫痫复发。聚类分析揭示了两个不同的聚类，每个聚类有86例患者。聚类2，我们定义为EMA加型，其特征为癫痫发作起始年龄较早、智力残疾发生率较高、EMA癫痫持续状态、广泛性阵发性快活动、自我诱发发作、FS以及ASM反应较差，而聚类1，即仅EMA聚类，其特征为癫痫发作缓解率较高且神经精神结局更有利。
讨论
癫痫发作早发是治疗反应不佳最相关的预后因素。观察到癫痫发作起始与ASM反应之间存在较长潜伏期，提示年龄相关的脑变化对EMA缓解的影响。最后，我们的聚类分析显示EMA患者明显分为EMA加型隐匿性亚表型和仅EMA良性聚类，在缓解率和认知结局方面有很大差异。
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